8 ms·

One Drug to Shrink All Tumors

187 points by ph0rque 15y ago

velus 15y ago
The real cancer cure is white blood cell transfusion. Check with LEF for more info (they are funding the trial). Certain Chinese doctors in China will perform it (under the cover), for those in need.
- hef19898 15y ago
  How do I like short comments like this. One cure and your cancer will go away. Yeah, right. And people actually might believe things like that with the result that they don't get proven treatment in time. Cancer is really serious, it can kill you you know, and since there are promising developments (as far as I can tell as not being a doctor), we are still far away from a definite cure to that. You would realy do everyone a favor by keeping comments like that for yourself.
  - ocdprogrammer 15y ago
    "You would realy do everyone a favor by keeping comments like that for yourself." Yeah, you too.
- andrewfelix 15y ago
  I'm going to ignore the HN guidelines and not be civil for a moment...You're an arsehole. Once you lose someone close to you from cancer you'll understand why.
hef19898 15y ago
Impressive with what kind of research and development scientist come up! Hope it works or at least helps.
fasteddie31003 15y ago
Here is my take on curing cancer from a programmers perspective. Extract a healthy strain of DNA from the patient, insert the healthy DNA into a virus that will be targeted to attack all cells of a certain type, which will include the cancerous cells. The erroneous/ cancerous will be replaced with the healthy DNA, while healthy cells get the DNA they already had. It's kinda like reformatting a hard drive. Has anyone heard of a custom treatment like this?
- bithive123 15y ago
  If you make enough simplifying assumptions anything is trivial.
  - Jimmie 15y ago
    Kill the cancer. Leave the normal tissue alone. C'mon scientists how hard can that be. /s
    - antihero 15y ago
      Surely we could just eventually breed microscopic dogs, and, you know, train them to sniff out and destroy the cancers?
- carbocation 15y ago
  > The erroneous/ cancerous will be replaced with the healthy DNA Human DNA, weighing in at gigabases, is too large to fit into viruses. Also, 'replacement' implies getting rid of the bad stuff, which isn't really explicitly contemplated here. Finally, if you are good enough at identifying cancer cells from the outside that you can target them for DNA replacement, you'll probably be better off by just killing that cell.
- Daniel_Newby 15y ago
  > ... a virus that will be targeted to attack all cells of a certain type ... The trouble is that living things are basically made of fancy Jello. There is no programmable interface to say "go here".
  - refurb 15y ago
    Actually, look up a company called Oncolytics. It's based around a technology that you can create viruses that only infect cancer cells. There is a lot of work going on in this area.
- dagw 15y ago
  As much as I hate to do this: http://xkcd.com/793/ http://xkcd.com/793/
andrewfelix 15y ago
"Weissman's team has received a $20 million grant from the California Institute for Regenerative Medicine" It's heartening to see this being properly funded.
frisco 15y ago
Wow. Extraordinary claims require extraordinary evidence, but Irv Weissman and his lab are the real deal. Here's the original article (which is open access): http://www.pnas.org/content/early/2012/03/20/1121623109 http://www.pnas.org/content/early/2012/03/20/1121623109 Of course, this isn't the first time we've seen such promising initial results only to hit roadblocks in translation, but here's to hoping it's a real effect, even if it eventually turns out to be less than a true "cure"! Edit: looks like this is follow-up work from Weissman's research on Leukemia, which is considered influential: http://www.cell.com/abstract/S0092-8674(09)00650-3 http://www.cell.com/abstract/S0092-8674(09)00650-3
- siganakis 15y ago
  The trouble is that there are many, many different ways that a cancerous cell is able to be cancerous. A malignant cancer cell has generally had upwards of 7 mutational events that directly enable it to replicate itself enough times to form a tumor and become damaging. These mutations includes things like breaking programmed cell death (apoptosis) pathways (e.g. P53 mutations), increases in anaerobic glycolysis (due to lack of oxygen within the micro-environment of a tumor), increasing production of angiogenesis related proteins (to create new blood vessels to the tumor so that it can continue to grow). Cancer cells even acquire mutations to the pathways that regulate DNA damage repair and replication so that further mutations happen more easily, providing more variation in the clonal colony of cancerous cells making the "cancer" more able to withstand changes in the tumors environment (e.g. the introduction of chemotherapy, hypoxia, etc). Essentially the cancer evolves over relatively short periods of time. In other words, this is just one pathway that there is a chance we may be able to disrupt, but it may very well be a crucial one. If we can build up enough drugs to target the specific mutations that make some cancers so aggressive, then we stand a good chance at significantly reducing the mortality of cancer. Excellent research, but we have a long way to go still.
  - Udo 15y ago
    Yes, however, the "drug" described (it's more of an idea for a drug at this stage, really) does not aim to disrupt the tumor cell itself. Instead it's based on the observation that many (maybe most?) cancerous cells over-express the protein CD47 on their surfaces as a survival mechanism in order to prevent macrophages and dendrites from taking them out. If successful - and that's a big if, because I'd be willing to wager this treatment will never see the light of day - if successful, the drug would break the CD47 recognition mechanism by blocking the protein with antibodies, thereby allowing the patient's immune system to attack the malfunctioning cells. In a way this would be more elegant than aiming at re-starting apoptosis pathways or blocking the expression of angiogenesis factors because the specific mechanisms employed by cancer cells to do so seem to vary greatly as you said.
wensing 15y ago
Why is it that I've read maybe a dozen articles like this in the past couple of years but still don't see much change in the way cancer is being treated in the wild? Will there be a year in the not-too-distant future when all of these breakthroughs finally hit the shelves? I realize the answer is "clinical trials take time and don't always work" but can someone please explain the process to me?
- frisco 15y ago
  First, there's a lot of bad science out there. A large part of this is due to the fact that animal models are almost uniformly terrible at modeling real human disease. Second, a therapy may be highly effective but also highly toxic or have other severe risks or side effects, which are hard to tell in preclinical research. The bar here is very high, and trials can easily be pulled over a few "adverse events." Third, it's rare that investigational drugs are used as first-line therapies; so, the patients getting them are usually the ones in worst shape. This can lead to all kinds of problems in demonstrating efficacy. Also, if your drug does get through trials, the FDA looks very hard at who the drug was tested on and can narrowly limit the indications it receives. So, if you develop "promising drug X", and it's trialled on Stage IV glioblastoma patients who express marker Y and are (for whatever reason) over the age of 45 and mostly female, then you're going to be limited to > 45 year old females with Stage IV glioblastoma expressing marker Y, until you can prove safety and efficacy in another population. But the vast majority of drugs never get anywhere near here: they mostly fail in safety or fail to demonstrate effectiveness early on. (An interesting side note here is that many of the signals you look for to estimate your "effectiveness", like size of tumor, don't always correlate to long-term survival. You can have a drug that appears to shrink tumors and patients still dying. It's really common to see good indicators of progress with little or no impact on survival.) TL;DR: animal models of disease mostly suck.
  - ekianjo 15y ago
    I agree with most of what you said, but for cancer drugs the adverse events are usually less critical for the development than for other drugs. Usually you conduct Ph1 in cancer patients instead of healthy volunteers for other therapeutic areas. Survival is the endpoint that matters, and adverse events are more regarded as a balance between risk and benefit for oncology. You would not accept the same kind of risks for a central nervous system drug, for example.
vibrunazo 15y ago
Anyone familiar with these could share some estimate of in about how much time can we expect to hear the results from human trials?
- refurb 15y ago
  Before even starting human trials they would need to do a bunch of pre-clinical work (pharmacokinetics, toxicology, etc). They could then get permission from the FDA to start phase I trials, which, depending on the type of cancer tested on, would probably take a couple years to turn around and get data on. My guess? 4-5 years?
suprgeek 15y ago
This is basically a neat hack - Cancerous cells use a certain Chemical marker to stop being attacked. This researcher blocks this marker from being used thus allowing the body's immune system to attack and destroy the Cancerous cells. This is very promising research indeed but while they have shown Human Tumor Cells in mice shrinking, they have yet to show Human cells in Humans shrinking. Should make for a very cool Phase-1 human trial.
- antihero 15y ago
  Isn't this marker also used by healthy cells? So what is to stop your system basically attacking itself massively?
  - suprgeek 15y ago
    I think the key is that Cancerous cells expressed a higher level of this marker leading the Immune cells to destroy them specifically. However there is also this line "Although macrophages also attacked blood cells expressing CD47 when mice were given the antibody, the researchers found that the decrease in blood cells was short-lived; the animals turned up production of new blood cells to replace those they lost from the treatment," so this seems like a very valid concern.
  - bedris 15y ago
    Good question. I'm an author on both of the new CD47 studies, so I'll try to answer this for you: 1. CD47 appears to be higher on tumor cells than on normal cells. In general, the higher the expression of a marker on a diseased cell versus a healthy cell, the more of a therapeutic window/index [1] that is available for a treatment to specifically target diseased cells. 2. Inhibiting the anti-phagocytosis (i.e., "don't eat me") signal is only half of the equation. There are also pro-phagocytosis (i.e., "eat me") signal(s) that also are present [2] and that play a role in whether, and how well, macrophages, and other phagocytes, can phagocytose a cell. "Eat me" signal(s) also differ between normal and cancer cells, adding more nuance to the situation. [1] Therapeutic index: http://en.wikipedia.org/wiki/Therapeutic_index http://en.wikipedia.org/wiki/Therapeutic_index [2] A paper examining a putative "eat me" signal, as it relates to CD47: http://stm.sciencemag.org/content/2/63/63ra94.abstract http://stm.sciencemag.org/content/2/63/63ra94.abstract
hirenj 15y ago
I'm not familiar enough with CD47 to know where else it is expressed, but I'm wondering what the "regular" use of CD47 is. Since it's over-expressed in cancers, I'm assuming the cancer is somehow mucking up the regulation pathway for CD47 and there are regular non-cancer related functions for CD47. The trick to making this work will be hoping that blocking CD47 on healthy cells isn't particularly lethal (in humans), or getting the antibody to target ONLY cancerous cells. edit: From the paper, it looks like the mice weren't unhappy with the antibody floating around - "Importantly, the therapeutic anti-mCD47 [antibody] produced no unacceptable toxicity over the course of the experiment, despite having spread systemically. These experiments were analyzed at the end of the therapeutic regimen; acute infusion of these antibodies led to a short-term anemia."
- frisco 15y ago
  Here you go: http://www.ncbi.nlm.nih.gov/protein?db=protein&cmd=link&linkname=protein_biosystems&uid=22713604 http://www.ncbi.nlm.nih.gov/protein?db=protein&cmd=link&... GenBank for CD47: http://www.ncbi.nlm.nih.gov/protein/AAH37306.1 http://www.ncbi.nlm.nih.gov/protein/AAH37306.1 (Should be obvious, but this is woefully incomplete in terms of where CD47 probably actually appears. But can be a good first place to start.)
  - hirenj 15y ago
    It turns out the first paragraph in the paper gives a good indication for me – it's pretty much all over the shop, which makes the lack of toxicity here pretty interesting.
amitutk 15y ago
I attended Dr Weisssman present this work a few years back at Dana-Farber. The somewhat long tl;dr is that while immune cells kill foreign material, normal cells have "don't eat me" signal, CD47, a cell surface marker. Cancer cells also have CD47, the "don't eat me" signal, which helps them evade the immune system. So, blocking CD47 would cause the immune system to naturally target the cancer cells, with minimal side effect. Weissman's lab has an excellent scientific record so this is as good as it is going to get. The challenge now is to see if these dynamics work the same way in humans.
- deleted 15y ago
  [deleted]
yogrish 15y ago
Thought HN might be interested in this very nice explanation on Cancer and some ways to prevent (to some extent) is shared by a redditor biochemist http://www.reddit.com/r/funny/comments/kb39j/scumbag_telomeres/c2iutkf http://www.reddit.com/r/funny/comments/kb39j/scumbag_telomer...

187 points by ph0rque 15y ago

velus 15y ago

The real cancer cure is white blood cell transfusion. Check with LEF for more info (they are funding the trial). Certain Chinese doctors in China will perform it (under the cover), for those in need.

hef19898 15y ago
How do I like short comments like this. One cure and your cancer will go away. Yeah, right. And people actually might believe things like that with the result that they don't get proven treatment in time. Cancer is really serious, it can kill you you know, and since there are promising developments (as far as I can tell as not being a doctor), we are still far away from a definite cure to that. You would realy do everyone a favor by keeping comments like that for yourself.
- ocdprogrammer 15y ago
  "You would realy do everyone a favor by keeping comments like that for yourself." Yeah, you too.
andrewfelix 15y ago
I'm going to ignore the HN guidelines and not be civil for a moment...You're an arsehole. Once you lose someone close to you from cancer you'll understand why.

hef19898 15y ago

Impressive with what kind of research and development scientist come up! Hope it works or at least helps.

fasteddie31003 15y ago

Here is my take on curing cancer from a programmers perspective. Extract a healthy strain of DNA from the patient, insert the healthy DNA into a virus that will be targeted to attack all cells of a certain type, which will include the cancerous cells. The erroneous/ cancerous will be replaced with the healthy DNA, while healthy cells get the DNA they already had. It's kinda like reformatting a hard drive. Has anyone heard of a custom treatment like this?

bithive123 15y ago
If you make enough simplifying assumptions anything is trivial.
- Jimmie 15y ago
  Kill the cancer. Leave the normal tissue alone. C'mon scientists how hard can that be. /s
  - antihero 15y ago
    Surely we could just eventually breed microscopic dogs, and, you know, train them to sniff out and destroy the cancers?
carbocation 15y ago
> The erroneous/ cancerous will be replaced with the healthy DNA Human DNA, weighing in at gigabases, is too large to fit into viruses. Also, 'replacement' implies getting rid of the bad stuff, which isn't really explicitly contemplated here. Finally, if you are good enough at identifying cancer cells from the outside that you can target them for DNA replacement, you'll probably be better off by just killing that cell.
Daniel_Newby 15y ago
> ... a virus that will be targeted to attack all cells of a certain type ... The trouble is that living things are basically made of fancy Jello. There is no programmable interface to say "go here".
- refurb 15y ago
  Actually, look up a company called Oncolytics. It's based around a technology that you can create viruses that only infect cancer cells. There is a lot of work going on in this area.
dagw 15y ago
As much as I hate to do this: http://xkcd.com/793/ http://xkcd.com/793/

andrewfelix 15y ago

"Weissman's team has received a $20 million grant from the California Institute for Regenerative Medicine" It's heartening to see this being properly funded.

frisco 15y ago

Wow. Extraordinary claims require extraordinary evidence, but Irv Weissman and his lab are the real deal. Here's the original article (which is open access): http://www.pnas.org/content/early/2012/03/20/1121623109 http://www.pnas.org/content/early/2012/03/20/1121623109 Of course, this isn't the first time we've seen such promising initial results only to hit roadblocks in translation, but here's to hoping it's a real effect, even if it eventually turns out to be less than a true "cure"! Edit: looks like this is follow-up work from Weissman's research on Leukemia, which is considered influential: http://www.cell.com/abstract/S0092-8674(09)00650-3 http://www.cell.com/abstract/S0092-8674(09)00650-3

siganakis 15y ago
The trouble is that there are many, many different ways that a cancerous cell is able to be cancerous. A malignant cancer cell has generally had upwards of 7 mutational events that directly enable it to replicate itself enough times to form a tumor and become damaging. These mutations includes things like breaking programmed cell death (apoptosis) pathways (e.g. P53 mutations), increases in anaerobic glycolysis (due to lack of oxygen within the micro-environment of a tumor), increasing production of angiogenesis related proteins (to create new blood vessels to the tumor so that it can continue to grow). Cancer cells even acquire mutations to the pathways that regulate DNA damage repair and replication so that further mutations happen more easily, providing more variation in the clonal colony of cancerous cells making the "cancer" more able to withstand changes in the tumors environment (e.g. the introduction of chemotherapy, hypoxia, etc). Essentially the cancer evolves over relatively short periods of time. In other words, this is just one pathway that there is a chance we may be able to disrupt, but it may very well be a crucial one. If we can build up enough drugs to target the specific mutations that make some cancers so aggressive, then we stand a good chance at significantly reducing the mortality of cancer. Excellent research, but we have a long way to go still.
- Udo 15y ago
  Yes, however, the "drug" described (it's more of an idea for a drug at this stage, really) does not aim to disrupt the tumor cell itself. Instead it's based on the observation that many (maybe most?) cancerous cells over-express the protein CD47 on their surfaces as a survival mechanism in order to prevent macrophages and dendrites from taking them out. If successful - and that's a big if, because I'd be willing to wager this treatment will never see the light of day - if successful, the drug would break the CD47 recognition mechanism by blocking the protein with antibodies, thereby allowing the patient's immune system to attack the malfunctioning cells. In a way this would be more elegant than aiming at re-starting apoptosis pathways or blocking the expression of angiogenesis factors because the specific mechanisms employed by cancer cells to do so seem to vary greatly as you said.

wensing 15y ago

Why is it that I've read maybe a dozen articles like this in the past couple of years but still don't see much change in the way cancer is being treated in the wild? Will there be a year in the not-too-distant future when all of these breakthroughs finally hit the shelves? I realize the answer is "clinical trials take time and don't always work" but can someone please explain the process to me?

frisco 15y ago
First, there's a lot of bad science out there. A large part of this is due to the fact that animal models are almost uniformly terrible at modeling real human disease. Second, a therapy may be highly effective but also highly toxic or have other severe risks or side effects, which are hard to tell in preclinical research. The bar here is very high, and trials can easily be pulled over a few "adverse events." Third, it's rare that investigational drugs are used as first-line therapies; so, the patients getting them are usually the ones in worst shape. This can lead to all kinds of problems in demonstrating efficacy. Also, if your drug does get through trials, the FDA looks very hard at who the drug was tested on and can narrowly limit the indications it receives. So, if you develop "promising drug X", and it's trialled on Stage IV glioblastoma patients who express marker Y and are (for whatever reason) over the age of 45 and mostly female, then you're going to be limited to > 45 year old females with Stage IV glioblastoma expressing marker Y, until you can prove safety and efficacy in another population. But the vast majority of drugs never get anywhere near here: they mostly fail in safety or fail to demonstrate effectiveness early on. (An interesting side note here is that many of the signals you look for to estimate your "effectiveness", like size of tumor, don't always correlate to long-term survival. You can have a drug that appears to shrink tumors and patients still dying. It's really common to see good indicators of progress with little or no impact on survival.) TL;DR: animal models of disease mostly suck.
- ekianjo 15y ago
  I agree with most of what you said, but for cancer drugs the adverse events are usually less critical for the development than for other drugs. Usually you conduct Ph1 in cancer patients instead of healthy volunteers for other therapeutic areas. Survival is the endpoint that matters, and adverse events are more regarded as a balance between risk and benefit for oncology. You would not accept the same kind of risks for a central nervous system drug, for example.

vibrunazo 15y ago

Anyone familiar with these could share some estimate of in about how much time can we expect to hear the results from human trials?

refurb 15y ago
Before even starting human trials they would need to do a bunch of pre-clinical work (pharmacokinetics, toxicology, etc). They could then get permission from the FDA to start phase I trials, which, depending on the type of cancer tested on, would probably take a couple years to turn around and get data on. My guess? 4-5 years?

suprgeek 15y ago

This is basically a neat hack - Cancerous cells use a certain Chemical marker to stop being attacked. This researcher blocks this marker from being used thus allowing the body's immune system to attack and destroy the Cancerous cells. This is very promising research indeed but while they have shown Human Tumor Cells in mice shrinking, they have yet to show Human cells in Humans shrinking. Should make for a very cool Phase-1 human trial.

antihero 15y ago
Isn't this marker also used by healthy cells? So what is to stop your system basically attacking itself massively?
- suprgeek 15y ago
  I think the key is that Cancerous cells expressed a higher level of this marker leading the Immune cells to destroy them specifically. However there is also this line "Although macrophages also attacked blood cells expressing CD47 when mice were given the antibody, the researchers found that the decrease in blood cells was short-lived; the animals turned up production of new blood cells to replace those they lost from the treatment," so this seems like a very valid concern.
- bedris 15y ago
  Good question. I'm an author on both of the new CD47 studies, so I'll try to answer this for you: 1. CD47 appears to be higher on tumor cells than on normal cells. In general, the higher the expression of a marker on a diseased cell versus a healthy cell, the more of a therapeutic window/index [1] that is available for a treatment to specifically target diseased cells. 2. Inhibiting the anti-phagocytosis (i.e., "don't eat me") signal is only half of the equation. There are also pro-phagocytosis (i.e., "eat me") signal(s) that also are present [2] and that play a role in whether, and how well, macrophages, and other phagocytes, can phagocytose a cell. "Eat me" signal(s) also differ between normal and cancer cells, adding more nuance to the situation. [1] Therapeutic index: http://en.wikipedia.org/wiki/Therapeutic_index http://en.wikipedia.org/wiki/Therapeutic_index [2] A paper examining a putative "eat me" signal, as it relates to CD47: http://stm.sciencemag.org/content/2/63/63ra94.abstract http://stm.sciencemag.org/content/2/63/63ra94.abstract

hirenj 15y ago

I'm not familiar enough with CD47 to know where else it is expressed, but I'm wondering what the "regular" use of CD47 is. Since it's over-expressed in cancers, I'm assuming the cancer is somehow mucking up the regulation pathway for CD47 and there are regular non-cancer related functions for CD47. The trick to making this work will be hoping that blocking CD47 on healthy cells isn't particularly lethal (in humans), or getting the antibody to target ONLY cancerous cells. edit: From the paper, it looks like the mice weren't unhappy with the antibody floating around - "Importantly, the therapeutic anti-mCD47 [antibody] produced no unacceptable toxicity over the course of the experiment, despite having spread systemically. These experiments were analyzed at the end of the therapeutic regimen; acute infusion of these antibodies led to a short-term anemia."

frisco 15y ago
Here you go: http://www.ncbi.nlm.nih.gov/protein?db=protein&cmd=link&linkname=protein_biosystems&uid=22713604 http://www.ncbi.nlm.nih.gov/protein?db=protein&cmd=link&... GenBank for CD47: http://www.ncbi.nlm.nih.gov/protein/AAH37306.1 http://www.ncbi.nlm.nih.gov/protein/AAH37306.1 (Should be obvious, but this is woefully incomplete in terms of where CD47 probably actually appears. But can be a good first place to start.)
- hirenj 15y ago
  It turns out the first paragraph in the paper gives a good indication for me – it's pretty much all over the shop, which makes the lack of toxicity here pretty interesting.

amitutk 15y ago

I attended Dr Weisssman present this work a few years back at Dana-Farber. The somewhat long tl;dr is that while immune cells kill foreign material, normal cells have "don't eat me" signal, CD47, a cell surface marker. Cancer cells also have CD47, the "don't eat me" signal, which helps them evade the immune system. So, blocking CD47 would cause the immune system to naturally target the cancer cells, with minimal side effect. Weissman's lab has an excellent scientific record so this is as good as it is going to get. The challenge now is to see if these dynamics work the same way in humans.

deleted 15y ago
[deleted]

yogrish 15y ago

Thought HN might be interested in this very nice explanation on Cancer and some ways to prevent (to some extent) is shared by a redditor biochemist http://www.reddit.com/r/funny/comments/kb39j/scumbag_telomeres/c2iutkf http://www.reddit.com/r/funny/comments/kb39j/scumbag_telomer...