5 ms·

Researchers Develop ‘Trojan Horse’ Drug That Tricks, Then Kills Cancer Cells

107 points by spking 7y ago

izuchukwu 7y ago
Paclitaxel, an existing chemotherapy agent, kills cancer by interfering with microtubule dynamics in cells, the same way that Fenbendazole and other antihelmintics (dewormers) attack cancer in the recent post about someone curing themselves by taking OTC dog dewormer [0]. Unlike the dog dewormer, today’s Paclitaxel regimens are quite toxic. Interestingly, most of the toxicity comes from the method of delivery [1], not the drug itself. It’s actually why the way we give it (infrequent doses) actually promotes recurrence in some cases. This post talks about a much less toxic method of delivery, which explains why they can up the dose of the drug significantly while still being much safer. [0]: https://news.ycombinator.com/item?id=20486893 https://news.ycombinator.com/item?id=20486893 [1]: https://en.m.wikipedia.org/wiki/Paclitaxel https://en.m.wikipedia.org/wiki/Paclitaxel
- headmelted 7y ago
  actually promotes recurrence in some cases With a therapeutic like the one described in the post I'd be really interested to know the cold, honest numbers on recurrence - not to be negative, just to understand where this falls with regards to other treatments. Obviously it can take years for recurrence rates to shake out and become evident, but I feel like in the last few years we've been hearing a lot about promising therapies (CAR-T, Harvard CD-47 trials, this) that ultimately fall off the common radar. It could be that these therapies are the real deal and are quietly saving lives now (I know CAR-T has shown real promise in liquid tumors), but it's worrying when news around this research falls silent as it makes it seem like they aren't providing lasting cures.
  - izuchukwu 7y ago
    Skepticism is very warranted here. And as I mention in your sibling comment, “promotes cancer recurrence” was a poor choice of term. “Permits,” due to the time between doses, would have been more accurate. There are a lot of fly-by-night stories like this for a variety of reasons, be it ongoing research, funding seeking, or otherwise. I do believe the Benzimidazole class of medication mentioned is worth taking a deeper look at however—it seems to be a common thread over many of these. Sometimes the reason something hasn’t seen use is more than the question of whether it’s clinically viable or not.
  - cannonedhamster 7y ago
    Some chemotherapy drugs list cancer as a possible side effect, which I thought was funny when they told me. Recurrence is different as it's generally hiding cancer "stem cells" that cause this. There's actually a drug in the works that attempts to activate these and make them more susceptible to standard chemo that I think is cool, but it's a few years before that reaches human trials. As for lasting results, most aren't cures, it's about improving the overall survivability, meaning time until the next treatment option opens up. A lot of these options give you a few months at most which is a big improvement and gives you a chance until the next thing comes out. The reason for this is that we're commonly talking about late stage cancers (3/4). Early stage cancers that haven't spread are cut out before they spread which is the best possible option as it's the highest likelihood of a cure.
- Gatsky 7y ago
  There are several inaccuracies in your comment. Infusion reactions to paclitaxel are rare and not serious. Most of the toxicity arises from cumulative nerve damage with chronic use. There is also no evidence it promotes cancer recurrence.
  - izuchukwu 7y ago
    I appreciate any & all correction—I’m still learning myself. I say toxic relative to the Benzimidazole family of medication, and though Paclitaxel’s worst side effects, like the neuropathy you mention, come cumulatively with chronic use, it’s more common side effects are still numerous, including a few serious ones, from sources I find. And “promotes cancer recurrence” was a poor choice of term on my part. What I mean here is the time between doses is wide enough to permit recurrence in some cases.
  - joadha 7y ago
    You better believe the infusion reactions can be serious, despite what any medical literature may be leading you to believe. My father went into anaphylaxis within minutes of his Taxol infusion. My family was kicked out of the treatment room while six medical workers stabilized him over the course of an afternoon.
    - cannonedhamster 7y ago
      My reaction wasn't as severe but I had a taxol based reaction as well. It's a barrel of fun, luckily mine was treatable with Benadryl. I don't envy you or your father.
- hanniabu 7y ago
  As an alternative, there have been successful tests where small amounts of polio is injected into the cancer so that the body can "see" it and attack it.
deleted 7y ago
[deleted]
aarbor989 7y ago
I feel like we hear about potential breakthrough cancer cures daily, but then never hear about them again. Do they not make it past animal testing or is our healthcare system so slow that it just takes forever for trials to move along?
- jdc 7y ago
  I think it's more that researchers frequently overstate the likelihood of their work leading to a cure and seldom publish negative results.
  - cannonedhamster 7y ago
    Actually they do publish most of the results, it's just negative results don't usually generate lots of press. With cancer patients it's typically late stage cancer patients on clinical trials, many/most of which die regardless of the treatment. A very positive treatment can be on the order of a few months of increased overall survivability on average. Typically this means some patients get a very positive result but most patients have so results either because they aren't a good match for the treatment or are too damaged to live longer anyways due to comorbidities. Unless you're constant following the studies you're unlikely to see the negative results.
- thefounder 7y ago
  I think the trials take "forever" time. Not to mention that they also cost "forever" money. If the investors or regulators are not convinced by the researchers you may say the "breakthrough" is DOA
  - cannonedhamster 7y ago
    Trials generally have a very specific time frame during the initial setup. Investors don't invest into specific treatments but into the companies, which can often make or break the company. With cancer trials typically this is a few years of studies at most. If results are promising they tend to move forward quickly, otherwise studies end prematurely for patient safety if negative outcome is seen. Neutral results are not uncommon.
chrisbennet 7y ago
Would the molecules cross the blood brain barrier? Is there a trial of this anywhere? (I have an inoperable brain tumor.)
- JBReefer 7y ago
  What’s that like? I’m sorry that happened to you.
  - chrisbennet 7y ago
    I’m happy and haven’t had to buy lunch in the last couple of months. :-) I’ve still got a year or so till it kills me. It is difficult on my wife, family and friends.
- izuchukwu 7y ago
  I’m not a doctor, this is very much not medical advice, and I’ve only been looking into these recently, but it does appear that the Benzimidazole class of medications from that recent cured-by-dog-dewormer post [0] like Albendazole and Mebendazole, both FDA approved as antihelmintics, do pass through the blood-brain barrier [1][2], and is currently used to that effect as a standard treatment for neurocysticercosis. It appears a neurosurgery professor at Johns Hopkins that independently discovered the link was interested in it for that very reason [3]. [0]: https://news.ycombinator.com/item?id=20486893 https://news.ycombinator.com/item?id=20486893 [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874411/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874411/ [2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403762/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403762/ [3]: https://www.npr.org/sections/health-shots/2017/01/30/512400204/a-pinworm-medication-is-being-tested-as-a-potential-anti-cancer-drug https://www.npr.org/sections/health-shots/2017/01/30/5124002...
  - chrisbennet 7y ago
    Thank you.
PakG1 7y ago
This language seems to be really gaining popularity. I believe this is the third or fourth time I've seen a cancer treatment referred to as a Trojan Horse. I have some stock in such a company, they're about to start Phase 2 clinical trials. It's a great time for cancer treatments in that I don't think there's ever been as much positivity as now about our chances to effectively treat various types of cancers. There's been lots of great progress. As someone who's father had to go through multiple cancer surgeries, I hope the day comes when we can consider cancer not much a bigger deal than the flu. Probably still a pipe dream, but it's a nice dream.
- rolltiide 7y ago
  Out of curiosity If your company is a for profit share company making inroads in this, then what is the point of donating money when the real progress seems to happens on the invested money looking for returns
  - cannonedhamster 7y ago
    You're typically donating to patient treatments, which are very expensive, and most treatment options don't work out long term if you're at the point where you're on clinical trials. There's also a lot of pure research into cancer itself.
  - PakG1 7y ago
    For profit companies can't spend funds on doing foundational research. There's no financial return on that. So foundational research is left to the universities and foundations. Biotech ventures only can focus on treatments.

107 points by spking 7y ago

Paclitaxel, an existing chemotherapy agent, kills cancer by interfering with microtubule dynamics in cells, the same way that Fenbendazole and other antihelmintics (dewormers) attack cancer in the recent post about someone curing themselves by taking OTC dog dewormer [0]. Unlike the dog dewormer, today’s Paclitaxel regimens are quite toxic. Interestingly, most of the toxicity comes from the method of delivery [1], not the drug itself. It’s actually why the way we give it (infrequent doses) actually promotes recurrence in some cases. This post talks about a much less toxic method of delivery, which explains why they can up the dose of the drug significantly while still being much safer. [0]: https://news.ycombinator.com/item?id=20486893 https://news.ycombinator.com/item?id=20486893 [1]: https://en.m.wikipedia.org/wiki/Paclitaxel https://en.m.wikipedia.org/wiki/Paclitaxel

headmelted 7y ago
actually promotes recurrence in some cases With a therapeutic like the one described in the post I'd be really interested to know the cold, honest numbers on recurrence - not to be negative, just to understand where this falls with regards to other treatments. Obviously it can take years for recurrence rates to shake out and become evident, but I feel like in the last few years we've been hearing a lot about promising therapies (CAR-T, Harvard CD-47 trials, this) that ultimately fall off the common radar. It could be that these therapies are the real deal and are quietly saving lives now (I know CAR-T has shown real promise in liquid tumors), but it's worrying when news around this research falls silent as it makes it seem like they aren't providing lasting cures.
- izuchukwu 7y ago
  Skepticism is very warranted here. And as I mention in your sibling comment, “promotes cancer recurrence” was a poor choice of term. “Permits,” due to the time between doses, would have been more accurate. There are a lot of fly-by-night stories like this for a variety of reasons, be it ongoing research, funding seeking, or otherwise. I do believe the Benzimidazole class of medication mentioned is worth taking a deeper look at however—it seems to be a common thread over many of these. Sometimes the reason something hasn’t seen use is more than the question of whether it’s clinically viable or not.
- cannonedhamster 7y ago
  Some chemotherapy drugs list cancer as a possible side effect, which I thought was funny when they told me. Recurrence is different as it's generally hiding cancer "stem cells" that cause this. There's actually a drug in the works that attempts to activate these and make them more susceptible to standard chemo that I think is cool, but it's a few years before that reaches human trials. As for lasting results, most aren't cures, it's about improving the overall survivability, meaning time until the next treatment option opens up. A lot of these options give you a few months at most which is a big improvement and gives you a chance until the next thing comes out. The reason for this is that we're commonly talking about late stage cancers (3/4). Early stage cancers that haven't spread are cut out before they spread which is the best possible option as it's the highest likelihood of a cure.
Gatsky 7y ago
There are several inaccuracies in your comment. Infusion reactions to paclitaxel are rare and not serious. Most of the toxicity arises from cumulative nerve damage with chronic use. There is also no evidence it promotes cancer recurrence.
- izuchukwu 7y ago
  I appreciate any & all correction—I’m still learning myself. I say toxic relative to the Benzimidazole family of medication, and though Paclitaxel’s worst side effects, like the neuropathy you mention, come cumulatively with chronic use, it’s more common side effects are still numerous, including a few serious ones, from sources I find. And “promotes cancer recurrence” was a poor choice of term on my part. What I mean here is the time between doses is wide enough to permit recurrence in some cases.
- joadha 7y ago
  You better believe the infusion reactions can be serious, despite what any medical literature may be leading you to believe. My father went into anaphylaxis within minutes of his Taxol infusion. My family was kicked out of the treatment room while six medical workers stabilized him over the course of an afternoon.
  - cannonedhamster 7y ago
    My reaction wasn't as severe but I had a taxol based reaction as well. It's a barrel of fun, luckily mine was treatable with Benadryl. I don't envy you or your father.
hanniabu 7y ago
As an alternative, there have been successful tests where small amounts of polio is injected into the cancer so that the body can "see" it and attack it.

deleted 7y ago

[deleted]

aarbor989 7y ago

I feel like we hear about potential breakthrough cancer cures daily, but then never hear about them again. Do they not make it past animal testing or is our healthcare system so slow that it just takes forever for trials to move along?

jdc 7y ago
I think it's more that researchers frequently overstate the likelihood of their work leading to a cure and seldom publish negative results.
- cannonedhamster 7y ago
  Actually they do publish most of the results, it's just negative results don't usually generate lots of press. With cancer patients it's typically late stage cancer patients on clinical trials, many/most of which die regardless of the treatment. A very positive treatment can be on the order of a few months of increased overall survivability on average. Typically this means some patients get a very positive result but most patients have so results either because they aren't a good match for the treatment or are too damaged to live longer anyways due to comorbidities. Unless you're constant following the studies you're unlikely to see the negative results.
thefounder 7y ago
I think the trials take "forever" time. Not to mention that they also cost "forever" money. If the investors or regulators are not convinced by the researchers you may say the "breakthrough" is DOA
- cannonedhamster 7y ago
  Trials generally have a very specific time frame during the initial setup. Investors don't invest into specific treatments but into the companies, which can often make or break the company. With cancer trials typically this is a few years of studies at most. If results are promising they tend to move forward quickly, otherwise studies end prematurely for patient safety if negative outcome is seen. Neutral results are not uncommon.

chrisbennet 7y ago

Would the molecules cross the blood brain barrier? Is there a trial of this anywhere? (I have an inoperable brain tumor.)

JBReefer 7y ago
What’s that like? I’m sorry that happened to you.
- chrisbennet 7y ago
  I’m happy and haven’t had to buy lunch in the last couple of months. :-) I’ve still got a year or so till it kills me. It is difficult on my wife, family and friends.
izuchukwu 7y ago
I’m not a doctor, this is very much not medical advice, and I’ve only been looking into these recently, but it does appear that the Benzimidazole class of medications from that recent cured-by-dog-dewormer post [0] like Albendazole and Mebendazole, both FDA approved as antihelmintics, do pass through the blood-brain barrier [1][2], and is currently used to that effect as a standard treatment for neurocysticercosis. It appears a neurosurgery professor at Johns Hopkins that independently discovered the link was interested in it for that very reason [3]. [0]: https://news.ycombinator.com/item?id=20486893 https://news.ycombinator.com/item?id=20486893 [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874411/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874411/ [2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403762/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403762/ [3]: https://www.npr.org/sections/health-shots/2017/01/30/512400204/a-pinworm-medication-is-being-tested-as-a-potential-anti-cancer-drug https://www.npr.org/sections/health-shots/2017/01/30/5124002...
- chrisbennet 7y ago
  Thank you.

PakG1 7y ago

This language seems to be really gaining popularity. I believe this is the third or fourth time I've seen a cancer treatment referred to as a Trojan Horse. I have some stock in such a company, they're about to start Phase 2 clinical trials. It's a great time for cancer treatments in that I don't think there's ever been as much positivity as now about our chances to effectively treat various types of cancers. There's been lots of great progress. As someone who's father had to go through multiple cancer surgeries, I hope the day comes when we can consider cancer not much a bigger deal than the flu. Probably still a pipe dream, but it's a nice dream.

rolltiide 7y ago
Out of curiosity If your company is a for profit share company making inroads in this, then what is the point of donating money when the real progress seems to happens on the invested money looking for returns
- cannonedhamster 7y ago
  You're typically donating to patient treatments, which are very expensive, and most treatment options don't work out long term if you're at the point where you're on clinical trials. There's also a lot of pure research into cancer itself.
- PakG1 7y ago
  For profit companies can't spend funds on doing foundational research. There's no financial return on that. So foundational research is left to the universities and foundations. Biotech ventures only can focus on treatments.