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Comment by frisco | Hacker News Reader

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

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

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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.

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.

Unfortunately, evolution is evolution, and if there is any way that cancer cells can trick the immune system that does not require CD47, trust me we'll know about it after the first few months using this drug. We've probably learned more about the intricate inner workings of cells by studying the ways in which cancers can evade treatments than by any other method. Still, I don't doubt this will be another tool in the oncologists tool belt and likely a useful one at that.

Is cancer cured? Not by a long shot!

What I find mildly disappointing is that cancer is an evolutionary process, but it is still treated primarily as a cell signaling disease. That is, everyone is studying how to attack individual cells. What we really need is a better understanding of the evolutionary process as a whole. Combination treatments are likely the correct solution, but which ones? in what doses? with what timing? Those are questions we need to answer.

  Unfortunately, evolution is evolution, and if there is any way that 
  cancer cells can trick the immune system that does not require CD47, 
  trust me we'll know about it after the first few months using this drug.

I totally agree. Also, I'm skeptical about side effects. We'll see. As I said, I don't believe this will come out as an actual drug.

  What I find mildly disappointing is that cancer is an evolutionary 
  process, but it is still treated primarily as a cell signaling disease.

Absolutely. We spend a lot of time figuring out the biochemical intricacies of very specialized tumor cells with, predictably, not a lot to show for it. My guess is we'll be making inroads this way as far as pre-cancerous and early stage disease is concerned but we simply lack the technology to deal with the phenomenon itself. To speculate further, I don't think this will be solved by micro-advancements in pharmaceuticals (even quite well-targeted ones), I believe we need a new class of active agent that can go in there and make decisions on a cell-by-cell basis if necessary.

Isn't the evolution of cancer cells rather more constrained than your average pathogen? A normal pathogen can infect many thousands or millions of hosts, and can evolve immunities over many years, decades or centuries. A cancer is limited to a single host, and cannot pass on any of its tricks; it must start from scratch each time.

If we had medicine as potent as penicillin that could attack or inhibit certain cancer cells, it might be that the cancer simply wouldn't have the time to fight back before it's removed entirely.

Cancer cells are rather more difficult to distinguish from normal cells than bacteria, of course, but it seems reasonable to assume we'd have less problems with cancer cells evolving defences.

One big difference between typical pathogens and cancer cells is that cancer cells have much more unstable genomes. Cancer cells divide rapidly and when they do, all sorts of mutations occur.

Even for someone with a diagnosed cancer (i.e. ovarian cancer), there are typically hundreds if not thousands of different types of cancer cells. This is what makes treating cancer so difficult. A drug may knock down 95% of your cancer, but the cells it didn't kill have no problem coming back and are now treatment-resistant.

There are plenty of drugs that work for cancer type A, B, C etc. Unfortunately, there are billions of people in the world all randomly generating Cancer's so all possible mutations are going to show up eventually in somebody.

Which presents the problem, let's say the most common 50% of all cancers are easily cured by drug X. Well the other 50% are all less common and moving to 100% is only going to get harder as you progress.

>>>Which presents the problem, let's say the most common 50% of all cancers are easily cured by drug X. Well the other 50% are all less common and moving to 100% is only going to get harder as you progress.

But for those who are in the 50% who can be cured in the first wave...

... and maybe one of them will go on to develop the cure that helps the remaining 50%.

But keep in mind each of those cancers is developing and evolving independently. Wiping out one type of cancer doesn't make it more likely for the other to proliferate on a population-wide scale. Sure, this treatment might not end up working for everyone, because some people's cancers might have developed chance resistance, but a whole bunch of people are going to be helped and cured without any ill evolutionary consequences.

Wait, how is this claim extraordinary? There's a proposed mechanism that doesn't seem to contradict anything we had previously thought we knew about biology, its not like researcher is claiming that he's found evidence for Lamarkian evolution or something.

We ask for extraordinary evidence for claims that are in and of themselves extraordinary. Simply having extraordinary implications doesn't warrant needing extraordinary evidence, though we should always be hesitant to rely on one person's experiments whether their claims are ordinary or not.

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