You're right, genetic diversity does matter, and maybe I'm a bit cavalier in saying if a drug doesn't work that means cancer is different. But I disagree that mechanism and treatment are distinct.
I would say that treatment and mechanism are related. Cancer has been "cured" in mice dozens of times and the reason those cures don't work in humans is not a dosage or a genetic issue. Rather it's that the drugs used while addressing a particular mechanism miss others. For example drugs that work great in mice for treating cancers with over-abundant EGF receptor also work in humans, but fail after a time because the cancer mutates in humans, but doesn't in mice. It's not a problem with the dose or the genetics, it's just that the mouse provides an incomplete picture.
While yes, mice and humans both develop cancers in senescence, most mouse models of cancer do not work this way because then out of a population of mice, you'd get a few old ones with cancer, and likely they'd be different kinds due to different causes. In other words, you'd have something that's hard to study and wouldn't give you much data as you would only have one or two examples of each particular cancer. Instead most mouse models are bred to be cancer prone, which gets to your genetics point. For the most part, humans aren't bred to be very cancer prone. The models they're talking about here are even worse, they're xenograft models. I.e. you take a tumor from a totally different organism, put it in that organism then see what happens. I think it's safe to say that people never get cancer by getting injected with a chimpanzee tumor.
Cancer is an extraordinarily complex disease. Genetically a mess, subtly different in every case, it's just really hard to study. And while animal models can help, I think it's hard to draw really strong conclusions from them, particularly in organisms that are very different in many ways. I'm just not convinced that zebrafish are a really good model going forward.
I guess my point about this article summarizes as cool trick, what for?
The real question to ask here is whether the spreading they observed has anything to do with how human cancers actually work.
1.) I think it's safe to say noone contracts cancer by getting injected with a tumor
2.) A melanoma (external skin cancer) would probably never originate inside the abdominal cavity. In other words, by implanting it you have already "metastasized" it.
and most importantly,
3.) It's a fish. It's not a human. It's not even a mammal. It's not even warm blooded. In other words, while its genetic code may not be too different on a DNA level, it's pretty gosh darned different from a human. Are the conclusions about how a human cancer evolves in a fish clinically relevant in humans. More to the point, will a fish's immune system deal with the spreading cells substantially differently than a human system. Given that genes important in embryonic development are often also oncogenes, does a model organism with a radically different developmental program really reflect how cancer operates in a human.
Bottom line: When mice subjected to the same kinds of experiments are treated with drug candidates, those drugs occasionally seem to work brilliantly. The mechanism of action for those candidates in some cases have been worked out, but still virtually none have any effect in humans. So, clearly, cancer does not work the same way in humans and mice. And mice are a whole lot more closely related to us than zebrafish are.
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You're right, genetic diversity does matter, and maybe I'm a bit cavalier in saying if a drug doesn't work that means cancer is different. But I disagree that mechanism and treatment are distinct.
I would say that treatment and mechanism are related. Cancer has been "cured" in mice dozens of times and the reason those cures don't work in humans is not a dosage or a genetic issue. Rather it's that the drugs used while addressing a particular mechanism miss others. For example drugs that work great in mice for treating cancers with over-abundant EGF receptor also work in humans, but fail after a time because the cancer mutates in humans, but doesn't in mice. It's not a problem with the dose or the genetics, it's just that the mouse provides an incomplete picture.
While yes, mice and humans both develop cancers in senescence, most mouse models of cancer do not work this way because then out of a population of mice, you'd get a few old ones with cancer, and likely they'd be different kinds due to different causes. In other words, you'd have something that's hard to study and wouldn't give you much data as you would only have one or two examples of each particular cancer. Instead most mouse models are bred to be cancer prone, which gets to your genetics point. For the most part, humans aren't bred to be very cancer prone. The models they're talking about here are even worse, they're xenograft models. I.e. you take a tumor from a totally different organism, put it in that organism then see what happens. I think it's safe to say that people never get cancer by getting injected with a chimpanzee tumor.
Cancer is an extraordinarily complex disease. Genetically a mess, subtly different in every case, it's just really hard to study. And while animal models can help, I think it's hard to draw really strong conclusions from them, particularly in organisms that are very different in many ways. I'm just not convinced that zebrafish are a really good model going forward.
I guess my point about this article summarizes as cool trick, what for?
The real question to ask here is whether the spreading they observed has anything to do with how human cancers actually work.
1.) I think it's safe to say noone contracts cancer by getting injected with a tumor
2.) A melanoma (external skin cancer) would probably never originate inside the abdominal cavity. In other words, by implanting it you have already "metastasized" it.
and most importantly,
3.) It's a fish. It's not a human. It's not even a mammal. It's not even warm blooded. In other words, while its genetic code may not be too different on a DNA level, it's pretty gosh darned different from a human. Are the conclusions about how a human cancer evolves in a fish clinically relevant in humans. More to the point, will a fish's immune system deal with the spreading cells substantially differently than a human system. Given that genes important in embryonic development are often also oncogenes, does a model organism with a radically different developmental program really reflect how cancer operates in a human.
Bottom line: When mice subjected to the same kinds of experiments are treated with drug candidates, those drugs occasionally seem to work brilliantly. The mechanism of action for those candidates in some cases have been worked out, but still virtually none have any effect in humans. So, clearly, cancer does not work the same way in humans and mice. And mice are a whole lot more closely related to us than zebrafish are.