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One Drug to Shrink All Tumors

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Re: One Drug to Shrink All Tumors

#11
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?

Re: One Drug to Shrink All Tumors

#12
post #11

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?

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.

Re: One Drug to Shrink All Tumors

#13
post #4
post #2

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.

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 eve…

"You would realy do everyone a favor by keeping comments like that for yourself." Yeah, you too.

Re: One Drug to Shrink All Tumors

#14
post #12
post #11

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?

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, i…

Wasn't too long, read and extremely interesting. A sincere thank you.

Cancer itself is such a rollercoaster of emotions for everyone involved and these promises and failures of breakthroughs are a sad and ironic parallel.

Re: One Drug to Shrink All Tumors

#16
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.

Re: One Drug to Shrink All Tumors

#17
post #12
post #11

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?

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, i…

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.

Re: One Drug to Shrink All Tumors

#18
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."

Re: One Drug to Shrink All Tumors

#19
post #18

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),…

Here you go: http://www.ncbi.nlm.nih.gov/protein?db=protein&cmd=link&...

GenBank for CD47: 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.)

Re: One Drug to Shrink All Tumors

#20
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.

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