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Comment by wensing | Hacker News Reader

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?

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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.

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.

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.

> you're going to be limited to > 45 year old females with Stage IV glioblastoma expressing marker Y

If the drug is approved for a specific use in a specific demographic, then doctors can choose to prescribe it for other uses and to other demographics. Apparently 50% of cancer patients receive an "off-label" drug: http://en.wikipedia.org/wiki/Off-label_use#Frequency_of_off-...

Cancer is a difficult biological problem. It is probably the most difficult biological problem I can think of, being both microscopic and inscrutable but also sharing features of population-scale problems. We use cancer as an analogy, but what is an analogy for cancer, apart from humanity itself?

It is easy to forget that most cancers develop through an evolutionary process that takes 15 - 20 years. During this time they are under constant selection pressure by the immune system.

It is not surprising therefore, that to turn up at the very end of the process when a patient has a civillization of heterogenous, optimised cancer growing in them that trying to eradicate the whole thing with a single approach, however elegant, is likely to fail. Cancer therapies in general provide an incremental benefit.

< 5% of therapies make it out of the lab into something a doctor can use on a patient who needs it.

There is just one more difficult biological problem; namely, death.

You read many articles like this because the press likes to latch onto every research finding and shout "Drug X / Prof Y cures cancer!"

In reality, cancer is many, many different diseases. About the only thing that cancers share is the property of uncontrolled (and unwanted) growth. Some of these cancers we already know how to cure, others remain incurable to date.

The reality is probably that there is no "cure for cancer", rather there are many, many individual treatments for specific cancers. Eventually, we may be able to tailor treatments to individual cancers but that's a long way away at the moment as I understand things.

"The Emperor of All Maladies" is a good read on the subject.

I used to think that, until I watched the TED talk by William Li [1]. The process of angiogenesis can be found as the catalyst in every cancer and medicine/food already work to reverse or halt angiogenesis. Doxycycline, for example, is a broad-spectrum anti-biotic that has been around for decades, is cheap and readily available and has been successful at slowing or regressing tumors. [2]

[1] http://www.ted.com/talks/william_li.html

[2] http://www.sunridgemedical.com/ResearchArticles/DoxycyclineC... (PDF)

Silver bullets usually aren't. (Sadly.)

Yeah, these drugs appear to improve survival times somewhat, but at extortionate expense.

Avastin for instance has been something of a disappointment: yes, it appears to delay mortality but that's about it & the FDA has pulled its approval for use in breast cancer because there was no evidence that it actually helped. The side effects can also be difficult, as you might expect for a drug that targets a process like blood vessel growth.

If dietary changes could have profound effects on cancer progression then a controlled trial would be simple (and ethically straightforward). In reality, eating a decent diet is known to reduce the rates of cancer & improve survival rates of those who are diagnosed with cancer, but it isn't a cure & it probably never will be.

There's a lot to be said for getting to the cancer before it takes off. Silver bullets are easy to dismiss, but what we're really talking about is stopping a simple process with a simple process. It would be hard to stop a missile once it's off the ground, but from the silo it's a matter of turning off a few switches - or rather, not allowing them to be turned on.

I don't claim to know medicine, but I am familiar with simple measures equating to great results when acting on initial factors. An ounce of prevention equals a pound of cure in this case.

> You read many articles like this because the press likes to latch onto every research finding and shout "Drug X / Prof Y cures cancer!"

http://www.phdcomics.com/comics.php?f=1174

Most of these grandiose announcements are composed in a way to secure funding for the research group releasing the paper in question. They are almost always entirely based on idealized animal models that have no hope of ever working in the real world. A very small percentage of these research ideas is viable and does make its way to clinical trials, after which these ideas are almost certainly buried never to be seen again due to a crushing load of patent concerns, hedging of liabilities, conflicts with corporate strategies, and general cultural resistance.

Pharmaceutical companies are doing a difficult tight rope walk here. On the one hand, they have a nice status quo, in essence a license to print money. On the other hand, they are subject to a number of threatening forces such as the expiry of patents or the ever-present danger of a rogue competitor making a disruptive discovery. This means there has to be a certain amount of innovation, and that innovation has to cost a lot of money, but ideally the improvements would be minimal. A lot of times, it makes way more sense to kill an idea and keep it under wraps. All big companies have to make these kinds of decisions, it's just good business sense.

Why hurry things up when the cancer treatment industry is making billions with the status quo?

I'm sure the industry (and by extension, the government regulatory and funding agencies) would rather this research was never funded in the first place.

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