Cancer’s Super-Survivors: How Immunotherapy Is Transforming Oncology | Hacker News Reader

Cancer’s Super-Survivors: How Immunotherapy Is Transforming Oncology

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75 pointslarrys13 comments

The article reports, "Most experts believe it will take combinations of immunotherapy drugs—or combinations of immunotherapy with other cancer treatments—to optimize their impact. But finding safe and effective combinations is a daunting undertaking." Yes. A lot of researchers, including researchers at companies that could commercialize applications of the latest research findings, are working on the general approach described in this interesting article, because the approach, if refined, promises substantial increase in healthy lifespan for many patients diagnosed with cancer. Making each patient's own immune system more responsive to cancerous cells looks like an important part of further advancing cancer treatment.

A key idea in medical treatment research is to look for an "endpoint" that actually matters for the patient. When the researchers looked for tumor shrinkage, they sometimes didn't find it soon enough to think that the patients were benefitting from treatment, but the patient Tom Telford named in the story reported feeling better during treatment, even when his tumor still appeared to be huge on scans of the tumor. When the researchers looked for the "hard endpoint" of patient survival, they found out these new treatments are better than they had realized at first. Proxy endpoints never beat hard endpoints in evaluating a treatment.

One more comment about how the story is presented. I will be really glad when doctors speaking to reporters, who are trying to talk in conversational, understandable language, and the reporters themselves get out of the habit of personifying or anthropomorphizing cancer cells, immune system cells, tumors, or even autonomous human body functions. Cancer cells and immune system cells are not knowing agents. They adapt (that is, successful cells survive while others die) but they don't "learn."

its not a big deal, your just caught up in language. in a sense learning is just adapting, 'successful' neurons propagate, less successful ones wither. also its helpful when thinking about these things to not fall for the fallacy that cancer and the immune system is simply cells - they are complex systems. For instance, the immune system does learn and adapt.

learning is a directed process with a target. the immune system is controled by the bervous system to reach that target, while cancer-cells, apparently are uncontrolled. there's a difference, although it matters more in an educational context.

Is there any indication that these treatments can help is prevention or return of metastatic rumors? (As someone going through treatment for stage iv colon cancer with liver metastasis. The erbitux has done wonders in shrinking the tumors, but there are serious skin toxicity issues that may require me to change regimes.)

Depends on how much the tumor mutates down the line. Most immunologic therapies and actions are based on specific markers antibodies can latch on to to mark cancer cells for destruction. With Cetusimab (generic name) you are already on a sort of immunologic treatment. It's a chimeric monoclonal antibody doing its antibody thing. Just taking a wild stab out to left field, the skin component of your reaction might be related to some sort of allergic-ish reaction to the mouse component of the cetusimab.

OK. I am not a doctor (just a PhD biochemistry)

I think that currently with these treatments complete remission is luck of the draw. Although many of these treatments (trastuzumab, cetuximab) were designed to block a growth factor from signalling on the cancer, what they ALSO seem to do is to recruit the immune system to the cancer and basically paint the cancer with a giant target.

Now, there is basically a competititon here; is your immune system powerful enough to kill the cancers painted by the antibodies faster than the cancer can adapt (usually by short-circuiting the growth signal). This sounds hokey, but for patients on these class of antibodies (ADCCs "antibody-directed, cell-mediated cytotoxicity"), I'd say it's important to keep a positive attitude, eliminate stress from one's life, and other things that strengthen the immune system. Unfortunately there are a lot of chemotherapeutics which are coadministered with these antibodies that throw a wrench into the immune system, as does radiation, etc.

As for the future, I think that there are some sneaky tricks that we can do to make ADCC drugs more powerful. Right now there is actually batch-to-batch variation in the power of these drugs, again going back to the 'luck of the draw'.

I also see some potential for ADC ("antibody-drug conjugate", not to be confused with ADCC) as well, this is attaching a warhead to an antibody and just directly killing the cells, although I think the ADCs that are being designed are not potent enough. But that is another story.

Finally, there will be a class of general chemotherapeutics that don't touch the immune system (I work on one through my nonprofit, there is one in Phase III - SJG-136) which I think will make for a nice 'sweeper' system to clean up any cells that have snuck out of whatever the antibody target is.

In short: I see a future where ADCCs are combined with ADCs and next-generation chemotherapeutics.

The other big challenge is that it's kind of very expensive to make antibody drugs. I think there are clever ways of bringing the cost down, and I might be working on that too.

This article hits close to home as my father had stage IV melanoma and took 2 rounds of Yervoy before becoming too sick and eventually passed away earlier this year. These drugs are very promising but the costs are absolutely ridiculous. $120,000 for four rounds (which is the initial amount you get before you must wait to complete more) is not viable for most people. Lucky my father has terrific insurance we paid maybe 10% of that cost. I did a lot of research on these drugs and there are some very severe side effects that you must watch out for. For most people these drugs are only slowing down the spread of the disease but by combining yervoy with other chemo drugs it can be very effective at treating melanoma.

but the costs are absolutely ridiculous. $120,000 for four rounds...

As the article details, it took 15 years to bring this drug to market, and the process has been and continues to be very research intensive. That money also pays for failures, it's not cheap to produce, and it's sold in small quantities for a currently small number of patients.

Yeah, it's not wonderful, but every time I hear that sort of thing, I also hear the sentiments that are (not so?) slowly shutting down new drug development.

You'll see this play out rather starkly as bacteria become continue to become more resistant to the usual antibiotics.

Just today, an early release in the finding of the immunotherapy drug nivolumab being use to treat non-Hodgkin's Lymphoma shows over 10% (4/29) of patients in complete remission. So I say that's pretty good. Dr. James Allison even said that for the 20-25% of patient that get an everlasting remission with Yervoy, that's great.

And those numbers will only go up.

Immunotherapy absolutely works for melanoma–I'm living proof. As a Stage IV melanoma survivor, immunotherapy via a tumor infiltrating lymphocytes (TIL) trial at NIH has extended (if not saved) my life. I'm over two years out from treatment and am currently NED (no evidence of disease).

Also, Federally-funded research at NIH continues to push the envelope at relegating cancer to a chronic disease (if not cured altogether).

“Death is not an option,” he told his doctor.

There's only one thing you have to do in life. Any you don't have to pay taxes.

Your defeatism is unbecoming.

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