16 ms·

A Universal Cancer Treatment?

383 points by WithinReason 4y ago

breck 4y ago
https://engeneic.com/intellectual-property/ https://engeneic.com/intellectual-property/ It's a scam.
nyx 4y ago
It really is remarkable how far cancer treatment has progressed, even in the last few years. I'm one of the unfortunate people who, through a close family encounter with cancer, knows more about this stuff than anyone should have to. The oncologist told my relative that if they had presented with this particular cancer just a decade ago, his recommendation would have been to start hospice care. However, in recent years, a very effective checkpoint inhibitor immunotherapy has been developed for the cancer in question. ~2x the success rates of traditional chemo, greatly increased overall survival statistics, and with massively reduced side effects. The results speak for themselves: this drug has granted my relative years of extra life in the worst case, and a path to a deep, long remission in the best case. I think that as the technology develops, by 2040 we'll be looking back at the present state of the art with the same incredulity that we currently have for, like, bloodletting with leeches in the Middle Ages. I think they've been saying this for a long time now, but it's truer than ever that a real cure for cancer is right around the corner.
- bongoman37 4y ago
  This. A close friend of mine was diagnosed with stage III stomach cancer. He lost massive amounts of weight and I almost thought he was not going to make it. And a year later he is back at work and doing pretty well.
- harmmonica 4y ago
  Would you be willing to share the type of cancer? Also, was the person you're referring to (can't tell if it was a relative) able to bypass traditional chemotherapy and go straight to the immunotherapy given the prognosis? Or did the oncologists require chemo first and only then your contact was able to receive the immunotherapy? Thanks for sharing anything you can. If more comfortable sharing in private, I can be reached at asuela1 at yahoo's email service (it's my spam account, but I'll check it if you tell me you wrote back there).
  - nyx 4y ago
    Stage IIIC NSCLC, specifically a superior sulcus tumor, advanced enough to be considered inoperable. Standard of care in this case was induction radiotherapy, followed by a single course of combination chemotherapy consisting of carboplatin, pemetrexed, and pembrolizumab (the last of which is the cutting-edge immunotherapy I'm talking about; brand name Keytruda.) After that, patients are prescribed the pemetrexed and immunotherapy alone for a long 2-year "maintenance" course, at which point treatment options will be reassessed. Surgery was not an option here because of the size and location of the mass, but after the initial course of chemo a PET-CT showed an 80% reduction in size. After some time on pembrolizumab, symptoms continue to improve and surgery may be back on the table soon. (edited for a more accurate picture of maintenance treatment; thanks to borbulon for refreshing my memory)
    - harmmonica 4y ago
      Thank you for pointing out the standard of care in this case, given inability to resect, was the immunotherapy from the start. Obviously very specific for that type of lung cancer and the state of your contact's tumor, but I've been learning more and more about this and have been told by multiple oncologists that immunotherapy is typically only given after more conventional treatments are first attempted and fail to stop progression or shrink the mass(es). Needless to say that's far from categorical so in my next conversations I can be a bit more educated in my questioning. And 80% reduction after that first course... Amazing. How long after the first course did they do the scan that showed that reduction? Btw, very happy for you (and even moreso for your contact). Great news.
      - clokar 4y ago
        Not sure about lung cancer, but there's positive results in other cancers for earlier immunotherapy ! https://oncologypro.esmo.org/meeting-resources/esmo-congress/neoadjuvant-immune-checkpoint-inhibition-in-locally-advanced-mmr-deficient-colon-cancer-the-niche-2-study https://oncologypro.esmo.org/meeting-resources/esmo-congress...
      - nyx 4y ago
- dominotw 4y ago
  > in recent years, a very effective checkpoint inhibitor immunotherapy has been developed for the cancer in question. ~2x the success rates of traditional chemo > I think they've been saying this for a long time now, but it's truer than ever that a real cure for cancer is right around the corner. I think thats quite a leap. For prostate cancer( most common cancer among men), top line therapies are still androgen blockage that was discover 70 yrs ago, chemo and radiation. Keytruda failed to deliver any significant survival benefits[1]. Yes we've gotten better at slash, burn , poison methods. Radiation is more trageted and sophisticated. Diagnostics are more precise. Chemo drugs have better safety profiles. But these are all marginal improvements. None of which indicate anything that we are close to a cure. Only hope we still have is to catch it earlier and go ham on it. Most of the slash,burn, poison methods are being FDA approved for earlier use. The other two things(one of which you've mentioned) are immune checkpoint blockade if you have MSI-hi/dMMR or PARP inhibition if you have BRCA2+. Even if you are lucky to have these mutations these drugs are a hit or miss[1]. I don't feel optimistic about a cure at all. 1. https://www.businesswire.com/news/home/20220803005334/en/Merck-Provides-Update-on-Phase-3-KEYNOTE-921-Trial-Evaluating-KEYTRUDA%C2%AE-pembrolizumab-Plus-Chemotherapy-in-Patients-With-Metastatic-Castration-Resistant-Prostate-Cancer https://www.businesswire.com/news/home/20220803005334/en/Mer...
  - nyx 4y ago
    I agree that my original comment is very optimistic--for what it's worth, Keytruda has thus far been very effective in the case I'm talking about, so I have some bias here. I concede that even in my "double the effectiveness" example, we're talking about doubling something like a 20% 5-year OS. By "around the corner" I'm really talking about, like, 20-30 years out, which I think is fairly soon in terms of cancer treatment progress. You're right that it reads like a leap in the context of my comment.
    - bnjemian 4y ago
      Not to be too pessimistic, but 600,000 people died of cancer in 2019, so 20-30 years is hardly "round the corner" when you extrapolate to the, let's say conservatively, 10 million families in the US losing loved ones in that time period. The history of cancer (The Emperor of All Maladies is a good book covering the history) is full of promising adjuvants, drugs, protocols that fail to generalize well. There are a lot of reasons for this. With drugs, one is that Phase 3 clinical trials often have patients who are selected on the basis of them being likely to be among the best responders. But once the drug is approved and made available to all patients within a given indication – a fundamentally different population – an overwhelming positive response may be significantly more modest. In many cases, this has to do with a patient's tolerance of the side effects or the interaction of the drug with known or underlying comorbidities. While I'm encouraged by the research in this article and could see the drug being part of a combination protocol, I'm hesitant that it will be "universal". And the mechanism, candidly, is downright scary – if I were running a Phase 3 for this (seems the trial cited was a Phase 2 demonstrating baseline safety in humans), I would want a very detailed articulation of how the technology ensures with a high margin of safety that the drug delivery is targeted to the tumor and no other tissues. The permeability of blood vessels in tumors would not be sufficient (and also does not seem "universal"). On a more personal note, I'm actually a computational biologist and have done quite a bit of work in cancer research (masters thesis, portion of my dissertation). My Mother was also diagnosed with a highly aggressive cancer of unknown primary (CUP) origin in her lung late last year (estimated stage IIIb for NSCLC, stage 4 for CUP/melanoma). Its location and heart involvement made it inoperable. Turned out is was a melanoma, which to be frank I quickly recognized down to the subtype upon reviewing the pathology reports. The lung oncologists were much more conservative; given the location, they weren't especially well-versed in melanoma, and presumed it was an adenocarcinoma with a rare presentation despite the staining for carcinomas being negative across the board. Luckily, we managed to convince them to split the difference on the standard of care – CarboTaxol (carboplatin + taxol) combination and immunotherapy (nivolumab and ipilimumab), all at once. The immunotherapy surely saved her life; unlike with carcinomas, chemo is roughly 5% effective (as in, any response whatsoever) for melanomas. About 70% of melanoma diagnoses respond to combination immunotherapy with about 15% going into full remission (memory is shaky on that last number, may be slightly higher). With >95 PDL-1 expression, she was one of the lucky ones – she had a full response on both imaging and pathological endpoints. That also made her tumor (or what was left of it) operable. She's two lobes and a chunk of heart lighter, but she's alive, healthy, and recovering well. And while I cringed when he did it, one of her oncologists dropped the "c word" after surgery in discussing her case. Knowing the foe, I'm much more cautious in contemplating whether any of this represents a cure. Psychologically, the uncertainty around the future maintains a heavy burden over her and our family. A 70% response rate sounds really good, but it's a very different calculus when you're living it. But as you said, her path towards a cure wouldn't have been possible not too long ago – in her case, 10-15 years; ipilimumab was approved in 2011 and nivolumab in 2014. But 30% of people with melanoma are still non-responders to combination immunotherapy. And, while a handful of other (generally less effective) options exist, non-responses in melanoma are deadly, often within a year or two of diagnosis, and for most all cancers have an incredibly high opportunity cost.
- borbulon 4y ago
  As a person who currently has stage IV NSCLC, I can add some context to this: YMMV. One thing to remember is that "Lung Cancer" is not just one thing. There are mutations of different genes, there are overexpressions of different genes. Each one has its own new medicines. Also, some peoples' cancers are more aggressive than others, and while for many they can find the right drug, for some nothing works. Keytruda works wonders for some. It did not for me. I had 4 treatments of the CPP (carboplatin, pemetrexed, and pembrolizumab) triad, which had some success. They then put you on "maintenance," which is the PP without the carboplatin (which is the really old school platinum-based chemo). Maintenance did nothing for me. My main tumor grew more than 50% in 2 months. Last summer I started 9 months on a chemo/immuno that was geared towards my specific mutation. It actually did wonders. It resulted in a 98% shrinkage of my main tumor before I ended up with pneumonitis from it and had to stop. But I've been able to be off treatment for the entire summer. I know there are others who have tried this, and it didn't work. So yeah, I'm really, really glad your relative was able to get some relief from the Keytruda. But I also wish it were the wonder cure for everyone that it was for them.
  - mromanuk 4y ago
    What are your thoughts on Dr. Seyfried and cancer as a metabolic disease?
  - tomcam 4y ago
    Shit. My best to you and yours. Thanks for sharing.
  - nyx 4y ago
    Thanks for sharing your story and treatment details. I should add that my relative's cancer has no particularly interesting mutations, but does have a high PD-L1 expression, which from what I can tell is the reason Keytruda was more likely to work for their situation. > that was geared towards my specific mutation This is actually one of the things that gives me hope for the future: genetic testing on a tissue sample of the patient's cancer is standard, and for many of the specific oncogenes that we know about, there exist therapies targeted to those specific mutations: https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/targeted-therapies.html https://www.cancer.org/cancer/lung-cancer/treating-non-small... One thing I've learned is that even in the face of good news, cancer is a horrible time, and I wouldn't wish it on anyone. But I'm likewise glad to hear about your results from the latest treatment, and hope things stay as positive as they can for you.
- asdff 4y ago
  As others have mentioned it depends. For instance the initial trials with pembrolizumab weren't the silver bullet the media makes them out to be today, until they identified what features might common among patients that did see a response, e.g. mismatch repair deficient cancers, because the tumor needs to be spitting out enough of these tumor-specific neoantigens to be targted by the immune system. That generally happens with highly mutated tumors such as those found in mismatch repair deficient tumors. The reason why the immune system was not targeting the tumors like it should have given the neoantigens until you take the drug is because the tumor cells presents the correct receptors that the immune system expects from healthy cells, which prevents the immune response. When you block that receptor as these drugs do, and also have many of these tumor specific neoantigens being expressed, then the immune system is able to target the tumor cells for death and the drug works well.
- silisili 4y ago
  It's moving so fast even doctors(sans oncologists, perhaps?) can't keep up. Brother's been a doctor about 15 years. Huge extended family is aging, and of course cancer creeps in. Of course family members call to get his opinion, and he's been wrong every single time(thankfully). Usually saying something like 'oh, she'll be dead within 2 years' and them living 6, or 8. And in one case calling something a death sentence that was actually, seemingly at least, cured. It's entirely possible he's just a shit doctor, but I like to think it's that progress has moved a ton since he's studied up on it last.
  - inglor_cz 4y ago
    It is also notable how doctors can get away with not following the progress in their own field. A programmer who would ignore the developments since 2007 would be unusable.
    - thelittleone 4y ago
      This 500x.
    - viraptor 4y ago
      "their field" is a fuzzy concept. For example for a GP their field is "medicine". By definition they need to know just enough about everything to direct you to a specialist when needed, but it's simply impossible to be up to date with everything. On the other hand, there's a huge number of consultants for enterprises which still write .net 4 like it's 2008 and they're both happy and productive. Unless they're sent to a training, why bother learning new stuff?
      - inglor_cz 4y ago
        True, but a GP shouldn't declare death sentences on their relatives if he is out of his depth in oncology.
    - biofox 4y ago
      I'm still programming in Java like it's 2001. No problems here :)
lwansbrough 4y ago
Did I miss it or was the delivery mechanism not really mentioned? I suppose that might be the secret sauce? What happens once they stop the growth of cancer, say in the case of a tumour? Will it break down over time or does it need to be surgically removed?
- axus 4y ago
  I think it was modified yeast bacteria produce a cell of exactly the right size to slip through the same blood vessels that the cancer did when it spread; unaffected blood vessels wouldn't let anything through.
- bottombutton 4y ago
  They genetically engineered a kind of bacteria that divides into non-living 'nanocells' that can't multiply further. These cells contain a special kind of RNA and a cell entry mechanism that lets them enter the cancer cells. The RNA interrupts the cell's ability to prepare for division. The article kind of implied that these nanocells follow the bloodstream pathways that cancer cells open when they metastasize. The researchers main concern was whether those nanoncells would also enter healthy cells, but the tests seem to show healthy cells were not affected.
Animats 4y ago
Has this been written up in some respected journal? (No, not Nature.)
- jjtheblunt 4y ago
  Their research was published in Cancer Cell. https://www.prnewswire.com/news-releases/engeneic-announces-publication-in-cancer-cell-of-a-scientific-paper-highlighting-the-ability-of-edv-nanocells-to-mount-dual-assault-on-cancer-cells-301024919.html https://www.prnewswire.com/news-releases/engeneic-announces-... https://engeneic.com/ https://engeneic.com/
- qclibre22 4y ago
  Othes by Stillman : https://scholar.google.com/citations?user=ANthHuAAAAAJ&hl=en&oi=ao https://scholar.google.com/citations?user=ANthHuAAAAAJ&hl=en...
Kalanos 4y ago
so this can put the breaks on cancer, but it can't fix cancer?
- notdonspaulding 4y ago
  I'm far from an expert, but my Dad is currently battling a high-grade glioblastoma multiforme tumor in his brain. So I've learned a little. > so this can put the breaks on cancer, but it can't fix cancer? "Putting the brakes on cancer" is basically equivalent to "fixing cancer". For my Dad's GBM, he has an MRI from 13 years before his diagnosis that seems to show the early stages of his tumor. At the time, his neuro noted that it was mildly concerning, but then didn't order any follow-up testing. So the tumor lay "dormant" in my Dad's head for over a decade. Then it started rapidly growing last year, until he was losing his balance at work, started getting scans, and eventually found the brain tumor. All of the standard of care around this is focused on mechanical or electromagnetic removal of large parts of the tumor, combined with throwing whatever chemotherapies you can at the body to stop the tumor from growing. Eventually, the tumor grows until it squeezes out all normal brain functionality. Anything that can arrest the tumor without killing you is good.
breck 4y ago
I ctrl+f for "patent" and got no hits, so forwarded it to someone on our team to dive in to further.
deleted 4y ago
[deleted]
Joel_Mckay 4y ago
It is not a single disease, but rather a result of several errant biological outcomes. The mortality rates have improved a lot with better treatments, and around 60% of the population will develop some form of the disease in their lifespan. The most disturbing part is most people are unaware they are ill until relatively late stages of the disease. If you live long enough, one will know many good people that go this way. It is a worthy area of research, as it improves the lives of many families. =)
- JanSt 4y ago
  Yes, my cancer was discovered pretty early by pure chance in a CT for an unrelated issue. I had zero symptoms, was really fit and pretty much never sick. Who knows how long it would have had time to mutate and grow otherwise. Early detection is a really important issue for cancer treatments.
- dominotw 4y ago
  liquid biopsy seems promising in early detection.
- heavyset_go 4y ago
  Screenings allowed my family members to catch cancer early when they still had chances for good prognoses, so don't skip out on regular checkups.
NetWonk_me 4y ago
Someday soon they'll look at our insane chemotherapy with the same level of utter disbelief as we do about bloodletting and tapeworm diets I mean untargeted chemotherapy kills -the one thing- that protects us since before we were born from cancer, our immune system. Killing our immune system to kill cancer makes as much sense as shooting off the leg you lead with so to run faster. Its idiotic, stupid and, yeah its basically trying to stop the copy errors in genes that cancer does, before all the massive amount of DNA errors kill the cancer victim ... It's like a really really bad CRISPR process as I understand it, like the computer program SED was majorly crapping out and it made your program an utter mess. Anyway, chemotherapy is DAMN foolish, and I for one will be glad when we're rid of it with better therapies
- slyrus 4y ago
  I'd argue that our future retrospective view of chemotherapy will be more of how we view hunting with a club rather than, say, a bow and arrow. Not optimal but, at least in many cases, proven to be better than nothing by multiple randomized clinical trials.
- sonofaragorn 4y ago
  If you got cancer and the onclogist recommended chemo, would you refuse it?
- adamredwoods 4y ago
  Nanoparticle-delivered chemotherapy could also be a potential solution, and is actively researched. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357073/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357073/
- d_tr 4y ago
  Invent something better if you know how. For many people chemo is their hope and in many cases does wonders by itself or in combination with other methods, either in parallel or in succession.
JanSt 4y ago
Does anyone know about updates on mRNA treatments for cancer? I had big hopes after the impressive corona-virus vaccines. I know BioNTech is investing heavily but not much has changed since then?
- sam537 4y ago
  There are a few vaccines that try to 'make' your immune system recognize an abnormal (read cancerous) protein as foreign (Sipleucel T for prostate, GMCSF vaccine for melanoma). Minimal activity.
yshrestha 4y ago
I may be missing something but the article does not explain how the bacteria target is actually targeting the cancer cells. Of course, if you can design an ideal universal cancer targeting mechanism, the active ingredient itself is beside the point. Did anyone else catch this? Stopping DNA replication across the body will be fatal. This is what eventually kills with radiation toxicity.
- asdff 4y ago
  It does, from the article: "“Normally, our blood vessel walls are all sealed pipes,” Brahmbhatt says. “But around wherever the cancer is growing, the blood vessels are known to be very defective. They have got a lot of holes in them.” Brahmbhatt and his collaborator Jennifer MacDiarmid devised a clever ploy. They would send a Trojan horse into malignant cells and turn cancer’s own trickery against it. The Trojan horse, in this case, is a product of a harmless bacteria that’s been genetically engineered to have specific qualities. When this genetically engineered bacteria divides, it yields a tiny non-living cell of 400 nanometers in diameter—the right size to slip through the damaged vessels and mingle with the tumors."
  - yshrestha 4y ago
    I see. I do wonder how specific that is though. Potentially it could be toxic to other areas where vasculature could be "leaky". Like in the filtration mechanisms in the kidney. Targeting the cancer's vascular supply is also a known anti-cancer mechanism of action (anti-angiogenics). How will this method not have the same toxicity as that one?
    - asdff 4y ago
      Presumably that 400nm size is important for specificity as well
- pazimzadeh 4y ago
  The article is missing lots of detail. They use antibodies to target receptors which are highly expressed by tumors, such as Epidermal growth factor receptor (EGFR). "Given that the EDV surface is coated with lipopolysaccharide (LPS), single-chain bispecific antibodies were attached to the EDV surface where one arm of the antibody is directed to the O-polysaccharide epitopes and the other arm is directed to a tumour cell surface receptor for example Epidermal growth factor receptor (EGFR) which is found on the surface of over 70% of solid tumours" and "The EDVs being 400 nm rapidly fall out of these fenestrations and enter into the tumour microenvironment and since they carry the bispecific antibody on the EDV surface, the anti-EGFR component binds to EGFR on the tumour cell surface. This provokes macropinocytosis and the EDVs are taken into the early endosomes, followed by lysosomes and broken down in these organelles releasing the drug PNU-159682. The drug enters into the tumour cell cytoplasm and the nucleus and intercalates with the chromosomal DNA resulting in tumour cell apoptosis. In the event that a tumour type does not express EGFR for example liver cancer, which expresses asialoglycoprotein, then the bispecific antibody can be changed to anti-asialoglycoprotein while the anti-O-polysaccharide component remains constant. Similarly, HER-2 positive breast cancers can be targeted via anti-HER2/anti-O-polysaccharide bispecific antibody" https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.13952 https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.111... I don't think this particular therapeutic automatically homes to all cancer cells. However, certain bacteria have been found to home to cancer cells, so maybe that helps too. https://wis-wander.weizmann.ac.il/life-sciences/cells-inside-cells-bacteria-live-cancer-cells https://wis-wander.weizmann.ac.il/life-sciences/cells-inside...
mentos 4y ago
Early detection? Whats the best way to detect cancer (money is no object) and how do we get that cost down 10x and get everyone to participate?
- chrisamiller 4y ago
  Money is absolutely an object. People are starting to do trials of early detection from circulating tumor DNA, and finding that the hit rate is alarmingly high. A decent portion of the population has some kind of malignancy, but most of these will either be cleared by the immune system, or be completely benign. Another problem is, if we detect this tumor DNA, it doesn't tell us where in the body the tumor might be. So then you're talking massive workups including while body CT scans and such for a problem that isn't going to be a problem for 99% of people. I'm not joking when I say that if rolled out as is, this has the potential to bankrupt the entire healthcare system with unnecessary procedures. To be clear, I very much think that early detection of tumors will someday be an essential part of cancer treatment. We are not there yet.
  - asdff 4y ago
    >Another problem is, if we detect this tumor DNA, it doesn't tell us where in the body the tumor might be. This isn't necessarily the case. A lot of CTCs have markers that are indicative of certain cancers or tissue types of origin. Different tissues have specific patterns of gene expression even if they all have the same underlying DNA, and there are databases with thousands of samples sequenced supporting these patterns.
  - Nathanael_M 4y ago
    I think the question being asked was "If money were no object, what is the best cancer detection method?", as opposed to stating that money wasn't an object. Very interesting comment, nonetheless.
  - mjsabby 4y ago
    Lots of clinics in Vancouver BC fully body MRI scans that are not super expensive. I really do think we should just make MRIs cheap and then get the whole world to do them. I understand the cost, time, etc. but I still think if we can stop doing other useless stuff as humanity and do this it would be net positive.
xchip 4y ago
Paper from a peer reviewed repo, not press releases please
sam537 4y ago
Oncologist here. You can think of drug development as an extremely wide funnel with a minuscule exit hole. At any given time a medium sized pharmaceutical company has 300-500 drug candidates. From this group 50 make it to phase 1 trials. 40 get slashed due to toxicity, company abandons them, gets bought by third party and sits in sleepy storage. 10 advance to phase 2 trials where 5-8 may not end up having enough efficacy/too toxic, does not improve survival. The remaining 3-5 advance to phase 3 where they can suffer the above as well. Tl:dr: Things usually work in the lab where all ideas start. Until a compound goes through thorough human experimentation believe little.
- nighthawk454 4y ago
  Thanks, that's an interesting insight into the dropoff rate for these ideas. Do you have an opinion on what the bottleneck is? Volume of ideas, length of testing, or perhaps flawed approach in general?
  - pfdietz 4y ago
    The extreme complexity of biology. There's no substitute to just trying things and seeing if they work, because you will never understand what's going on beforehand.
    - dominotw 4y ago
      funny how many of blockebuster drugs were discovered by accident.
      - pfdietz 4y ago
        And for some that were designed to hit a specific target, it was discovered afterwards that they work by a completely different mechanism.
  - sam537 4y ago
    This is the bottleneck for one company. We have many companies this size doing the same thing. The issue is large companies (novartis/BMS) sometimes sit on compounds and refuse to develop because they think it may not be worth it, may think a certain disease (read market) is saturated, or they may be waiting for the 'right time'. It can be frustrating. Smaller companies have 2-3 compounds which they actively work to develop but most of them end up getting acquired by the big fish.
nikivi 4y ago
I loved Michael Levin's thoughts on solving cancer. Kind of similar to immunotherapy but on a level of reprogramming the cells back that got 'lost' from their big purpose in their organ. https://www.youtube.com/watch?v=p3lsYlod5OU&t=8653s https://www.youtube.com/watch?v=p3lsYlod5OU&t=8653s
- ncmncm 4y ago
  Michael Levin is an astonishing breath of fresh air.
bulbosaur123 4y ago
When could we realistically see this solution for someone with prostate cancer?
Lytic42 4y ago
Some quick thoughts. This therapy uses a combination of methods that are already used in oncology. The usage of bacteria in oncology as part of immunotherapies has existed for decades via the use of BCG, although it is notably that these bacteria have genetic modifications to allow it to create a delivery vehicle as well. siRNAs have always been an attractive method but lacked proper delivery methods and initially had issues with degradation. The knockdown of DNA polymerases is new to me. Typically chemotherapeutics are anti-metabolites or seek to arrest mitosis (taxanes for example lock part of the cytoskeleton [microtubules] needed to move chromosomes). Targeting DNA polymerase makes fundamentally more sense because you would by and large avoid disrupting other cellular functions. Hopefully this represents another tool in the kit in regards to conjugate/combination therapies like Trastuzumab-deruxtecan. Quick question: Based on this statements would these therapy work particularly well against metastatic disease given its moa for cell selectivity?
echelon 4y ago
The universal cancer treatment will be full body transplant. As long as the cancer isn't in the patient's brain, the patient's head could be removed and transplanted onto a donor (brain dead) body. This would render the patient a quadriplegic, but with repeated study over decades we might be able to repair the nervous system. There isn't a large set of brain dead bodies to draw from, so if this process proves successful, perhaps we could one day start growing human bodies in labs from a monoclonal source. If we remove their ABO and MHC antigens, we might be able to lessen the need for an ongoing life-altering immunosuppressant regimen. These lab grown bodies would be headless/brainless from the outset via gene and surgical deactivation during development to remove any ethical issues. The bodies could be artificially innervated and pumped with the hormonal signals they need to grow until it's time to harvest them. Cancer is thousands and thousands of different disease states, and it will remain a difficult landscape for the foreseeable future. A non-molecular approach of wholesale cancer tissue removal (via body replacement) seems like an out of the box solution that could work.
wonder_er 4y ago
I can't help but mention that there are two dominant schools of thought regarding cancer treatments: 1. The Somatic theory of cancer ('bad genes/out-of-control cellular replication') 2. The metabolic theory of cancer ('cancer cells ferment blood sugar for energy via an ancient emergency metabolic pathway') Both have merit, but a complete occlusion of one would be bad. I wrote an open letter, long ago, to a wealthy person who was on the board of a cancer research center, suggesting they read a book and fund the key research scientist: https://josh.works/mike-clayville-can-have-a-huge-impact-on-cancer https://josh.works/mike-clayville-can-have-a-huge-impact-on-... I thought of the metabolic theory of cancer as I opened this page, because all cancers have a similar reliance upon certain energy generation pathways, which implies a corresponding vulnerability for treatment. Some people find it interesting enough to click through, read the article, and to read the book.
- uwuemu 4y ago
  > cancer cells ferment blood sugar oh boy
  - deleted 4y ago
    [deleted]
  - devinj 4y ago
    They do. Eg https://www.cancer.gov/research/key-initiatives/ras/ras-central/blog/2021/vander-heiden-warburg-effect https://www.cancer.gov/research/key-initiatives/ras/ras-cent... Obviously not usually considered cause, but rather effect.
  - tyingq 4y ago
    It's why PET scans work well on cancer patients, they inject you with a glucose analog that has a radioactive marker.
Gatsky 4y ago
Here is the only clinical data: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4632 https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.46... Looks as promising as any other promising cancer therapy in phase I trials! There is a renaissance in cancer drug delivery at present, exemplified by antibody drug conjugates. The tech in the article is very interesting, and a superb bioengineering effort. A caveat is that complex multi-unit therapies don’t have a great track record. They are hard to manufacture reliably, and have a very large optimisation volume, so it’s difficult to increment the development as you only have finite resources for human trials. Contrast this with small molecules where there is a well defined process over various chemical and pharmacokinetic factors, prior to testing in humans. We also lack a good system for developing and trialing ‘platform’ tech like this - the current system is set up for single drugs/combos to be tested and eventually reimbursed in each cancer type separately. If you have a platform for delivering tailored therapies agnostic of cancer type, you will run into many barriers. There is currently only one drug I know of simultaneously approved across multiple cancer types (pembrolizumab in mismatch repair deficient tumours, a rare population). So many challenges ahead of the hype here.
adamredwoods 4y ago
The article reminds me of the cowpea mosaic virus, a similar hope that seems to force the immune system to attack the cancer: https://www.dartmouth-hitchcock.org/stories/article/norris-cotton-cancer-center-researchers-discover-how-plant-virus-activates-immune-system https://www.dartmouth-hitchcock.org/stories/article/norris-c... https://www.bloomberg.com/press-releases/2022-02-02/newly-published-data-further-support-mosaic-immunoengineering-s-lead-immuno-oncology-candidate-mie-101-in-combination https://www.bloomberg.com/press-releases/2022-02-02/newly-pu...
Subsentient 4y ago
Watch all the funding dry up and the researcher get framed for some random, stupid crime, with just enough prison time to make sure he won't see the inside of a lab again before he's too senile to use it or dead. Could also be a slip in the tub etc. There's a lot of money in suffering, and if you think there aren't people sick enough out there to do real horrible shit to protect that income stream, you're kidding yourself. How do you think this fucked up civilization was twisted into the giant pulsating tumor it currently is?

383 points by WithinReason 4y ago

https://engeneic.com/intellectual-property/ https://engeneic.com/intellectual-property/ It's a scam.

nyx 4y ago

It really is remarkable how far cancer treatment has progressed, even in the last few years. I'm one of the unfortunate people who, through a close family encounter with cancer, knows more about this stuff than anyone should have to. The oncologist told my relative that if they had presented with this particular cancer just a decade ago, his recommendation would have been to start hospice care. However, in recent years, a very effective checkpoint inhibitor immunotherapy has been developed for the cancer in question. ~2x the success rates of traditional chemo, greatly increased overall survival statistics, and with massively reduced side effects. The results speak for themselves: this drug has granted my relative years of extra life in the worst case, and a path to a deep, long remission in the best case. I think that as the technology develops, by 2040 we'll be looking back at the present state of the art with the same incredulity that we currently have for, like, bloodletting with leeches in the Middle Ages. I think they've been saying this for a long time now, but it's truer than ever that a real cure for cancer is right around the corner.

bongoman37 4y ago
This. A close friend of mine was diagnosed with stage III stomach cancer. He lost massive amounts of weight and I almost thought he was not going to make it. And a year later he is back at work and doing pretty well.
harmmonica 4y ago
Would you be willing to share the type of cancer? Also, was the person you're referring to (can't tell if it was a relative) able to bypass traditional chemotherapy and go straight to the immunotherapy given the prognosis? Or did the oncologists require chemo first and only then your contact was able to receive the immunotherapy? Thanks for sharing anything you can. If more comfortable sharing in private, I can be reached at asuela1 at yahoo's email service (it's my spam account, but I'll check it if you tell me you wrote back there).
- nyx 4y ago
  Stage IIIC NSCLC, specifically a superior sulcus tumor, advanced enough to be considered inoperable. Standard of care in this case was induction radiotherapy, followed by a single course of combination chemotherapy consisting of carboplatin, pemetrexed, and pembrolizumab (the last of which is the cutting-edge immunotherapy I'm talking about; brand name Keytruda.) After that, patients are prescribed the pemetrexed and immunotherapy alone for a long 2-year "maintenance" course, at which point treatment options will be reassessed. Surgery was not an option here because of the size and location of the mass, but after the initial course of chemo a PET-CT showed an 80% reduction in size. After some time on pembrolizumab, symptoms continue to improve and surgery may be back on the table soon. (edited for a more accurate picture of maintenance treatment; thanks to borbulon for refreshing my memory)
  - harmmonica 4y ago
    Thank you for pointing out the standard of care in this case, given inability to resect, was the immunotherapy from the start. Obviously very specific for that type of lung cancer and the state of your contact's tumor, but I've been learning more and more about this and have been told by multiple oncologists that immunotherapy is typically only given after more conventional treatments are first attempted and fail to stop progression or shrink the mass(es). Needless to say that's far from categorical so in my next conversations I can be a bit more educated in my questioning. And 80% reduction after that first course... Amazing. How long after the first course did they do the scan that showed that reduction? Btw, very happy for you (and even moreso for your contact). Great news.
    - clokar 4y ago
      Not sure about lung cancer, but there's positive results in other cancers for earlier immunotherapy ! https://oncologypro.esmo.org/meeting-resources/esmo-congress/neoadjuvant-immune-checkpoint-inhibition-in-locally-advanced-mmr-deficient-colon-cancer-the-niche-2-study https://oncologypro.esmo.org/meeting-resources/esmo-congress...
    - nyx 4y ago
dominotw 4y ago
> in recent years, a very effective checkpoint inhibitor immunotherapy has been developed for the cancer in question. ~2x the success rates of traditional chemo > I think they've been saying this for a long time now, but it's truer than ever that a real cure for cancer is right around the corner. I think thats quite a leap. For prostate cancer( most common cancer among men), top line therapies are still androgen blockage that was discover 70 yrs ago, chemo and radiation. Keytruda failed to deliver any significant survival benefits[1]. Yes we've gotten better at slash, burn , poison methods. Radiation is more trageted and sophisticated. Diagnostics are more precise. Chemo drugs have better safety profiles. But these are all marginal improvements. None of which indicate anything that we are close to a cure. Only hope we still have is to catch it earlier and go ham on it. Most of the slash,burn, poison methods are being FDA approved for earlier use. The other two things(one of which you've mentioned) are immune checkpoint blockade if you have MSI-hi/dMMR or PARP inhibition if you have BRCA2+. Even if you are lucky to have these mutations these drugs are a hit or miss[1]. I don't feel optimistic about a cure at all. 1. https://www.businesswire.com/news/home/20220803005334/en/Merck-Provides-Update-on-Phase-3-KEYNOTE-921-Trial-Evaluating-KEYTRUDA%C2%AE-pembrolizumab-Plus-Chemotherapy-in-Patients-With-Metastatic-Castration-Resistant-Prostate-Cancer https://www.businesswire.com/news/home/20220803005334/en/Mer...
- nyx 4y ago
  I agree that my original comment is very optimistic--for what it's worth, Keytruda has thus far been very effective in the case I'm talking about, so I have some bias here. I concede that even in my "double the effectiveness" example, we're talking about doubling something like a 20% 5-year OS. By "around the corner" I'm really talking about, like, 20-30 years out, which I think is fairly soon in terms of cancer treatment progress. You're right that it reads like a leap in the context of my comment.
  - bnjemian 4y ago
    Not to be too pessimistic, but 600,000 people died of cancer in 2019, so 20-30 years is hardly "round the corner" when you extrapolate to the, let's say conservatively, 10 million families in the US losing loved ones in that time period. The history of cancer (The Emperor of All Maladies is a good book covering the history) is full of promising adjuvants, drugs, protocols that fail to generalize well. There are a lot of reasons for this. With drugs, one is that Phase 3 clinical trials often have patients who are selected on the basis of them being likely to be among the best responders. But once the drug is approved and made available to all patients within a given indication – a fundamentally different population – an overwhelming positive response may be significantly more modest. In many cases, this has to do with a patient's tolerance of the side effects or the interaction of the drug with known or underlying comorbidities. While I'm encouraged by the research in this article and could see the drug being part of a combination protocol, I'm hesitant that it will be "universal". And the mechanism, candidly, is downright scary – if I were running a Phase 3 for this (seems the trial cited was a Phase 2 demonstrating baseline safety in humans), I would want a very detailed articulation of how the technology ensures with a high margin of safety that the drug delivery is targeted to the tumor and no other tissues. The permeability of blood vessels in tumors would not be sufficient (and also does not seem "universal"). On a more personal note, I'm actually a computational biologist and have done quite a bit of work in cancer research (masters thesis, portion of my dissertation). My Mother was also diagnosed with a highly aggressive cancer of unknown primary (CUP) origin in her lung late last year (estimated stage IIIb for NSCLC, stage 4 for CUP/melanoma). Its location and heart involvement made it inoperable. Turned out is was a melanoma, which to be frank I quickly recognized down to the subtype upon reviewing the pathology reports. The lung oncologists were much more conservative; given the location, they weren't especially well-versed in melanoma, and presumed it was an adenocarcinoma with a rare presentation despite the staining for carcinomas being negative across the board. Luckily, we managed to convince them to split the difference on the standard of care – CarboTaxol (carboplatin + taxol) combination and immunotherapy (nivolumab and ipilimumab), all at once. The immunotherapy surely saved her life; unlike with carcinomas, chemo is roughly 5% effective (as in, any response whatsoever) for melanomas. About 70% of melanoma diagnoses respond to combination immunotherapy with about 15% going into full remission (memory is shaky on that last number, may be slightly higher). With >95 PDL-1 expression, she was one of the lucky ones – she had a full response on both imaging and pathological endpoints. That also made her tumor (or what was left of it) operable. She's two lobes and a chunk of heart lighter, but she's alive, healthy, and recovering well. And while I cringed when he did it, one of her oncologists dropped the "c word" after surgery in discussing her case. Knowing the foe, I'm much more cautious in contemplating whether any of this represents a cure. Psychologically, the uncertainty around the future maintains a heavy burden over her and our family. A 70% response rate sounds really good, but it's a very different calculus when you're living it. But as you said, her path towards a cure wouldn't have been possible not too long ago – in her case, 10-15 years; ipilimumab was approved in 2011 and nivolumab in 2014. But 30% of people with melanoma are still non-responders to combination immunotherapy. And, while a handful of other (generally less effective) options exist, non-responses in melanoma are deadly, often within a year or two of diagnosis, and for most all cancers have an incredibly high opportunity cost.
borbulon 4y ago
As a person who currently has stage IV NSCLC, I can add some context to this: YMMV. One thing to remember is that "Lung Cancer" is not just one thing. There are mutations of different genes, there are overexpressions of different genes. Each one has its own new medicines. Also, some peoples' cancers are more aggressive than others, and while for many they can find the right drug, for some nothing works. Keytruda works wonders for some. It did not for me. I had 4 treatments of the CPP (carboplatin, pemetrexed, and pembrolizumab) triad, which had some success. They then put you on "maintenance," which is the PP without the carboplatin (which is the really old school platinum-based chemo). Maintenance did nothing for me. My main tumor grew more than 50% in 2 months. Last summer I started 9 months on a chemo/immuno that was geared towards my specific mutation. It actually did wonders. It resulted in a 98% shrinkage of my main tumor before I ended up with pneumonitis from it and had to stop. But I've been able to be off treatment for the entire summer. I know there are others who have tried this, and it didn't work. So yeah, I'm really, really glad your relative was able to get some relief from the Keytruda. But I also wish it were the wonder cure for everyone that it was for them.
- mromanuk 4y ago
  What are your thoughts on Dr. Seyfried and cancer as a metabolic disease?
- tomcam 4y ago
  Shit. My best to you and yours. Thanks for sharing.
- nyx 4y ago
  Thanks for sharing your story and treatment details. I should add that my relative's cancer has no particularly interesting mutations, but does have a high PD-L1 expression, which from what I can tell is the reason Keytruda was more likely to work for their situation. > that was geared towards my specific mutation This is actually one of the things that gives me hope for the future: genetic testing on a tissue sample of the patient's cancer is standard, and for many of the specific oncogenes that we know about, there exist therapies targeted to those specific mutations: https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/targeted-therapies.html https://www.cancer.org/cancer/lung-cancer/treating-non-small... One thing I've learned is that even in the face of good news, cancer is a horrible time, and I wouldn't wish it on anyone. But I'm likewise glad to hear about your results from the latest treatment, and hope things stay as positive as they can for you.
asdff 4y ago
As others have mentioned it depends. For instance the initial trials with pembrolizumab weren't the silver bullet the media makes them out to be today, until they identified what features might common among patients that did see a response, e.g. mismatch repair deficient cancers, because the tumor needs to be spitting out enough of these tumor-specific neoantigens to be targted by the immune system. That generally happens with highly mutated tumors such as those found in mismatch repair deficient tumors. The reason why the immune system was not targeting the tumors like it should have given the neoantigens until you take the drug is because the tumor cells presents the correct receptors that the immune system expects from healthy cells, which prevents the immune response. When you block that receptor as these drugs do, and also have many of these tumor specific neoantigens being expressed, then the immune system is able to target the tumor cells for death and the drug works well.
silisili 4y ago
It's moving so fast even doctors(sans oncologists, perhaps?) can't keep up. Brother's been a doctor about 15 years. Huge extended family is aging, and of course cancer creeps in. Of course family members call to get his opinion, and he's been wrong every single time(thankfully). Usually saying something like 'oh, she'll be dead within 2 years' and them living 6, or 8. And in one case calling something a death sentence that was actually, seemingly at least, cured. It's entirely possible he's just a shit doctor, but I like to think it's that progress has moved a ton since he's studied up on it last.
- inglor_cz 4y ago
  It is also notable how doctors can get away with not following the progress in their own field. A programmer who would ignore the developments since 2007 would be unusable.
  - thelittleone 4y ago
    This 500x.
  - viraptor 4y ago
    "their field" is a fuzzy concept. For example for a GP their field is "medicine". By definition they need to know just enough about everything to direct you to a specialist when needed, but it's simply impossible to be up to date with everything. On the other hand, there's a huge number of consultants for enterprises which still write .net 4 like it's 2008 and they're both happy and productive. Unless they're sent to a training, why bother learning new stuff?
    - inglor_cz 4y ago
      True, but a GP shouldn't declare death sentences on their relatives if he is out of his depth in oncology.
  - biofox 4y ago
    I'm still programming in Java like it's 2001. No problems here :)

lwansbrough 4y ago

Did I miss it or was the delivery mechanism not really mentioned? I suppose that might be the secret sauce? What happens once they stop the growth of cancer, say in the case of a tumour? Will it break down over time or does it need to be surgically removed?

axus 4y ago
I think it was modified yeast bacteria produce a cell of exactly the right size to slip through the same blood vessels that the cancer did when it spread; unaffected blood vessels wouldn't let anything through.
bottombutton 4y ago
They genetically engineered a kind of bacteria that divides into non-living 'nanocells' that can't multiply further. These cells contain a special kind of RNA and a cell entry mechanism that lets them enter the cancer cells. The RNA interrupts the cell's ability to prepare for division. The article kind of implied that these nanocells follow the bloodstream pathways that cancer cells open when they metastasize. The researchers main concern was whether those nanoncells would also enter healthy cells, but the tests seem to show healthy cells were not affected.

Animats 4y ago

Has this been written up in some respected journal? (No, not Nature.)

jjtheblunt 4y ago
Their research was published in Cancer Cell. https://www.prnewswire.com/news-releases/engeneic-announces-publication-in-cancer-cell-of-a-scientific-paper-highlighting-the-ability-of-edv-nanocells-to-mount-dual-assault-on-cancer-cells-301024919.html https://www.prnewswire.com/news-releases/engeneic-announces-... https://engeneic.com/ https://engeneic.com/
qclibre22 4y ago
Othes by Stillman : https://scholar.google.com/citations?user=ANthHuAAAAAJ&hl=en&oi=ao https://scholar.google.com/citations?user=ANthHuAAAAAJ&hl=en...

Kalanos 4y ago

so this can put the breaks on cancer, but it can't fix cancer?

notdonspaulding 4y ago
I'm far from an expert, but my Dad is currently battling a high-grade glioblastoma multiforme tumor in his brain. So I've learned a little. > so this can put the breaks on cancer, but it can't fix cancer? "Putting the brakes on cancer" is basically equivalent to "fixing cancer". For my Dad's GBM, he has an MRI from 13 years before his diagnosis that seems to show the early stages of his tumor. At the time, his neuro noted that it was mildly concerning, but then didn't order any follow-up testing. So the tumor lay "dormant" in my Dad's head for over a decade. Then it started rapidly growing last year, until he was losing his balance at work, started getting scans, and eventually found the brain tumor. All of the standard of care around this is focused on mechanical or electromagnetic removal of large parts of the tumor, combined with throwing whatever chemotherapies you can at the body to stop the tumor from growing. Eventually, the tumor grows until it squeezes out all normal brain functionality. Anything that can arrest the tumor without killing you is good.

breck 4y ago

I ctrl+f for "patent" and got no hits, so forwarded it to someone on our team to dive in to further.

deleted 4y ago

[deleted]

Joel_Mckay 4y ago

It is not a single disease, but rather a result of several errant biological outcomes. The mortality rates have improved a lot with better treatments, and around 60% of the population will develop some form of the disease in their lifespan. The most disturbing part is most people are unaware they are ill until relatively late stages of the disease. If you live long enough, one will know many good people that go this way. It is a worthy area of research, as it improves the lives of many families. =)

JanSt 4y ago
Yes, my cancer was discovered pretty early by pure chance in a CT for an unrelated issue. I had zero symptoms, was really fit and pretty much never sick. Who knows how long it would have had time to mutate and grow otherwise. Early detection is a really important issue for cancer treatments.
dominotw 4y ago
liquid biopsy seems promising in early detection.
heavyset_go 4y ago
Screenings allowed my family members to catch cancer early when they still had chances for good prognoses, so don't skip out on regular checkups.

NetWonk_me 4y ago

Someday soon they'll look at our insane chemotherapy with the same level of utter disbelief as we do about bloodletting and tapeworm diets I mean untargeted chemotherapy kills -the one thing- that protects us since before we were born from cancer, our immune system. Killing our immune system to kill cancer makes as much sense as shooting off the leg you lead with so to run faster. Its idiotic, stupid and, yeah its basically trying to stop the copy errors in genes that cancer does, before all the massive amount of DNA errors kill the cancer victim ... It's like a really really bad CRISPR process as I understand it, like the computer program SED was majorly crapping out and it made your program an utter mess. Anyway, chemotherapy is DAMN foolish, and I for one will be glad when we're rid of it with better therapies

slyrus 4y ago
I'd argue that our future retrospective view of chemotherapy will be more of how we view hunting with a club rather than, say, a bow and arrow. Not optimal but, at least in many cases, proven to be better than nothing by multiple randomized clinical trials.
sonofaragorn 4y ago
If you got cancer and the onclogist recommended chemo, would you refuse it?
adamredwoods 4y ago
Nanoparticle-delivered chemotherapy could also be a potential solution, and is actively researched. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357073/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357073/
d_tr 4y ago
Invent something better if you know how. For many people chemo is their hope and in many cases does wonders by itself or in combination with other methods, either in parallel or in succession.

JanSt 4y ago

Does anyone know about updates on mRNA treatments for cancer? I had big hopes after the impressive corona-virus vaccines. I know BioNTech is investing heavily but not much has changed since then?

sam537 4y ago
There are a few vaccines that try to 'make' your immune system recognize an abnormal (read cancerous) protein as foreign (Sipleucel T for prostate, GMCSF vaccine for melanoma). Minimal activity.

yshrestha 4y ago

I may be missing something but the article does not explain how the bacteria target is actually targeting the cancer cells. Of course, if you can design an ideal universal cancer targeting mechanism, the active ingredient itself is beside the point. Did anyone else catch this? Stopping DNA replication across the body will be fatal. This is what eventually kills with radiation toxicity.

asdff 4y ago
It does, from the article: "“Normally, our blood vessel walls are all sealed pipes,” Brahmbhatt says. “But around wherever the cancer is growing, the blood vessels are known to be very defective. They have got a lot of holes in them.” Brahmbhatt and his collaborator Jennifer MacDiarmid devised a clever ploy. They would send a Trojan horse into malignant cells and turn cancer’s own trickery against it. The Trojan horse, in this case, is a product of a harmless bacteria that’s been genetically engineered to have specific qualities. When this genetically engineered bacteria divides, it yields a tiny non-living cell of 400 nanometers in diameter—the right size to slip through the damaged vessels and mingle with the tumors."
- yshrestha 4y ago
  I see. I do wonder how specific that is though. Potentially it could be toxic to other areas where vasculature could be "leaky". Like in the filtration mechanisms in the kidney. Targeting the cancer's vascular supply is also a known anti-cancer mechanism of action (anti-angiogenics). How will this method not have the same toxicity as that one?
  - asdff 4y ago
    Presumably that 400nm size is important for specificity as well
pazimzadeh 4y ago
The article is missing lots of detail. They use antibodies to target receptors which are highly expressed by tumors, such as Epidermal growth factor receptor (EGFR). "Given that the EDV surface is coated with lipopolysaccharide (LPS), single-chain bispecific antibodies were attached to the EDV surface where one arm of the antibody is directed to the O-polysaccharide epitopes and the other arm is directed to a tumour cell surface receptor for example Epidermal growth factor receptor (EGFR) which is found on the surface of over 70% of solid tumours" and "The EDVs being 400 nm rapidly fall out of these fenestrations and enter into the tumour microenvironment and since they carry the bispecific antibody on the EDV surface, the anti-EGFR component binds to EGFR on the tumour cell surface. This provokes macropinocytosis and the EDVs are taken into the early endosomes, followed by lysosomes and broken down in these organelles releasing the drug PNU-159682. The drug enters into the tumour cell cytoplasm and the nucleus and intercalates with the chromosomal DNA resulting in tumour cell apoptosis. In the event that a tumour type does not express EGFR for example liver cancer, which expresses asialoglycoprotein, then the bispecific antibody can be changed to anti-asialoglycoprotein while the anti-O-polysaccharide component remains constant. Similarly, HER-2 positive breast cancers can be targeted via anti-HER2/anti-O-polysaccharide bispecific antibody" https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.13952 https://sfamjournals.onlinelibrary.wiley.com/doi/full/10.111... I don't think this particular therapeutic automatically homes to all cancer cells. However, certain bacteria have been found to home to cancer cells, so maybe that helps too. https://wis-wander.weizmann.ac.il/life-sciences/cells-inside-cells-bacteria-live-cancer-cells https://wis-wander.weizmann.ac.il/life-sciences/cells-inside...

mentos 4y ago

Early detection? Whats the best way to detect cancer (money is no object) and how do we get that cost down 10x and get everyone to participate?

chrisamiller 4y ago
Money is absolutely an object. People are starting to do trials of early detection from circulating tumor DNA, and finding that the hit rate is alarmingly high. A decent portion of the population has some kind of malignancy, but most of these will either be cleared by the immune system, or be completely benign. Another problem is, if we detect this tumor DNA, it doesn't tell us where in the body the tumor might be. So then you're talking massive workups including while body CT scans and such for a problem that isn't going to be a problem for 99% of people. I'm not joking when I say that if rolled out as is, this has the potential to bankrupt the entire healthcare system with unnecessary procedures. To be clear, I very much think that early detection of tumors will someday be an essential part of cancer treatment. We are not there yet.
- asdff 4y ago
  >Another problem is, if we detect this tumor DNA, it doesn't tell us where in the body the tumor might be. This isn't necessarily the case. A lot of CTCs have markers that are indicative of certain cancers or tissue types of origin. Different tissues have specific patterns of gene expression even if they all have the same underlying DNA, and there are databases with thousands of samples sequenced supporting these patterns.
- Nathanael_M 4y ago
  I think the question being asked was "If money were no object, what is the best cancer detection method?", as opposed to stating that money wasn't an object. Very interesting comment, nonetheless.
- mjsabby 4y ago
  Lots of clinics in Vancouver BC fully body MRI scans that are not super expensive. I really do think we should just make MRIs cheap and then get the whole world to do them. I understand the cost, time, etc. but I still think if we can stop doing other useless stuff as humanity and do this it would be net positive.

xchip 4y ago

Paper from a peer reviewed repo, not press releases please

sam537 4y ago

Oncologist here. You can think of drug development as an extremely wide funnel with a minuscule exit hole. At any given time a medium sized pharmaceutical company has 300-500 drug candidates. From this group 50 make it to phase 1 trials. 40 get slashed due to toxicity, company abandons them, gets bought by third party and sits in sleepy storage. 10 advance to phase 2 trials where 5-8 may not end up having enough efficacy/too toxic, does not improve survival. The remaining 3-5 advance to phase 3 where they can suffer the above as well. Tl:dr: Things usually work in the lab where all ideas start. Until a compound goes through thorough human experimentation believe little.

nighthawk454 4y ago
Thanks, that's an interesting insight into the dropoff rate for these ideas. Do you have an opinion on what the bottleneck is? Volume of ideas, length of testing, or perhaps flawed approach in general?
- pfdietz 4y ago
  The extreme complexity of biology. There's no substitute to just trying things and seeing if they work, because you will never understand what's going on beforehand.
  - dominotw 4y ago
    funny how many of blockebuster drugs were discovered by accident.
    - pfdietz 4y ago
      And for some that were designed to hit a specific target, it was discovered afterwards that they work by a completely different mechanism.
- sam537 4y ago
  This is the bottleneck for one company. We have many companies this size doing the same thing. The issue is large companies (novartis/BMS) sometimes sit on compounds and refuse to develop because they think it may not be worth it, may think a certain disease (read market) is saturated, or they may be waiting for the 'right time'. It can be frustrating. Smaller companies have 2-3 compounds which they actively work to develop but most of them end up getting acquired by the big fish.

nikivi 4y ago

I loved Michael Levin's thoughts on solving cancer. Kind of similar to immunotherapy but on a level of reprogramming the cells back that got 'lost' from their big purpose in their organ. https://www.youtube.com/watch?v=p3lsYlod5OU&t=8653s https://www.youtube.com/watch?v=p3lsYlod5OU&t=8653s

ncmncm 4y ago
Michael Levin is an astonishing breath of fresh air.

bulbosaur123 4y ago

When could we realistically see this solution for someone with prostate cancer?

Lytic42 4y ago

Some quick thoughts. This therapy uses a combination of methods that are already used in oncology. The usage of bacteria in oncology as part of immunotherapies has existed for decades via the use of BCG, although it is notably that these bacteria have genetic modifications to allow it to create a delivery vehicle as well. siRNAs have always been an attractive method but lacked proper delivery methods and initially had issues with degradation. The knockdown of DNA polymerases is new to me. Typically chemotherapeutics are anti-metabolites or seek to arrest mitosis (taxanes for example lock part of the cytoskeleton [microtubules] needed to move chromosomes). Targeting DNA polymerase makes fundamentally more sense because you would by and large avoid disrupting other cellular functions. Hopefully this represents another tool in the kit in regards to conjugate/combination therapies like Trastuzumab-deruxtecan. Quick question: Based on this statements would these therapy work particularly well against metastatic disease given its moa for cell selectivity?

echelon 4y ago

The universal cancer treatment will be full body transplant. As long as the cancer isn't in the patient's brain, the patient's head could be removed and transplanted onto a donor (brain dead) body. This would render the patient a quadriplegic, but with repeated study over decades we might be able to repair the nervous system. There isn't a large set of brain dead bodies to draw from, so if this process proves successful, perhaps we could one day start growing human bodies in labs from a monoclonal source. If we remove their ABO and MHC antigens, we might be able to lessen the need for an ongoing life-altering immunosuppressant regimen. These lab grown bodies would be headless/brainless from the outset via gene and surgical deactivation during development to remove any ethical issues. The bodies could be artificially innervated and pumped with the hormonal signals they need to grow until it's time to harvest them. Cancer is thousands and thousands of different disease states, and it will remain a difficult landscape for the foreseeable future. A non-molecular approach of wholesale cancer tissue removal (via body replacement) seems like an out of the box solution that could work.

wonder_er 4y ago

I can't help but mention that there are two dominant schools of thought regarding cancer treatments: 1. The Somatic theory of cancer ('bad genes/out-of-control cellular replication') 2. The metabolic theory of cancer ('cancer cells ferment blood sugar for energy via an ancient emergency metabolic pathway') Both have merit, but a complete occlusion of one would be bad. I wrote an open letter, long ago, to a wealthy person who was on the board of a cancer research center, suggesting they read a book and fund the key research scientist: https://josh.works/mike-clayville-can-have-a-huge-impact-on-cancer https://josh.works/mike-clayville-can-have-a-huge-impact-on-... I thought of the metabolic theory of cancer as I opened this page, because all cancers have a similar reliance upon certain energy generation pathways, which implies a corresponding vulnerability for treatment. Some people find it interesting enough to click through, read the article, and to read the book.

uwuemu 4y ago
> cancer cells ferment blood sugar oh boy
- deleted 4y ago
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- devinj 4y ago
  They do. Eg https://www.cancer.gov/research/key-initiatives/ras/ras-central/blog/2021/vander-heiden-warburg-effect https://www.cancer.gov/research/key-initiatives/ras/ras-cent... Obviously not usually considered cause, but rather effect.
- tyingq 4y ago
  It's why PET scans work well on cancer patients, they inject you with a glucose analog that has a radioactive marker.

Gatsky 4y ago

Here is the only clinical data: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4632 https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.46... Looks as promising as any other promising cancer therapy in phase I trials! There is a renaissance in cancer drug delivery at present, exemplified by antibody drug conjugates. The tech in the article is very interesting, and a superb bioengineering effort. A caveat is that complex multi-unit therapies don’t have a great track record. They are hard to manufacture reliably, and have a very large optimisation volume, so it’s difficult to increment the development as you only have finite resources for human trials. Contrast this with small molecules where there is a well defined process over various chemical and pharmacokinetic factors, prior to testing in humans. We also lack a good system for developing and trialing ‘platform’ tech like this - the current system is set up for single drugs/combos to be tested and eventually reimbursed in each cancer type separately. If you have a platform for delivering tailored therapies agnostic of cancer type, you will run into many barriers. There is currently only one drug I know of simultaneously approved across multiple cancer types (pembrolizumab in mismatch repair deficient tumours, a rare population). So many challenges ahead of the hype here.

adamredwoods 4y ago

The article reminds me of the cowpea mosaic virus, a similar hope that seems to force the immune system to attack the cancer: https://www.dartmouth-hitchcock.org/stories/article/norris-cotton-cancer-center-researchers-discover-how-plant-virus-activates-immune-system https://www.dartmouth-hitchcock.org/stories/article/norris-c... https://www.bloomberg.com/press-releases/2022-02-02/newly-published-data-further-support-mosaic-immunoengineering-s-lead-immuno-oncology-candidate-mie-101-in-combination https://www.bloomberg.com/press-releases/2022-02-02/newly-pu...

Subsentient 4y ago

Watch all the funding dry up and the researcher get framed for some random, stupid crime, with just enough prison time to make sure he won't see the inside of a lab again before he's too senile to use it or dead. Could also be a slip in the tub etc. There's a lot of money in suffering, and if you think there aren't people sick enough out there to do real horrible shit to protect that income stream, you're kidding yourself. How do you think this fucked up civilization was twisted into the giant pulsating tumor it currently is?