James P. Allison

I think it's a plague of a sort that unfortunately involves your own body going awry in some way. And a lot of, I don't know, there used to be a lot of stigma associated with it. Maybe there still is in some cases. But it's an unfortunate thing that happens to us. We have a lot of cells that comprise our body. If they don't aren't controlled.

I think it's a plague of a sort that unfortunately involves your own body going awry in some way. And a lot of, I don't know, there used to be a lot of stigma associated with it. Maybe there still is in some cases. But it's an unfortunate thing that happens to us. We have a lot of cells that comprise our body. If they don't aren't controlled.

It's amazing to me that it works as well as it does, that everything stays under control. Unfortunately, it hits people. It hits a lot of people, way too many. It's hit way too many in my family.

It's amazing to me that it works as well as it does, that everything stays under control. Unfortunately, it hits people. It hits a lot of people, way too many. It's hit way too many in my family.

No, it's not. Well, it depends. I mean, the common thing is the cells growing when they ought not to and where they ought not to. I mean, that's the common thing of all of them. But no, they're very different. They're different tissues. First of all, that's why it used to be classified solid, you know, and muscle or whatever solid tissue versus leukemias, you know, in the blood.

No, it's not. Well, it depends. I mean, the common thing is the cells growing when they ought not to and where they ought not to. I mean, that's the common thing of all of them. But no, they're very different. They're different tissues. First of all, that's why it used to be classified solid, you know, and muscle or whatever solid tissue versus leukemias, you know, in the blood.

And then now it's lung versus, you know, colon or bladder versus prostate or whatever. But then with the advent of genomic sequencing and everything, the tendency was to attribute them to the causation. First, crudely, obviously carcinogen-induced and obviously virus-induced or something, although viruses are a tiny fraction of it. It's not zero, but that's not the main thing.

And then now it's lung versus, you know, colon or bladder versus prostate or whatever. But then with the advent of genomic sequencing and everything, the tendency was to attribute them to the causation. First, crudely, obviously carcinogen-induced and obviously virus-induced or something, although viruses are a tiny fraction of it. It's not zero, but that's not the main thing.

But the common thing is just mutation. the functional classification according to causation can be useful, and for a while it was thought was the real key.

But the common thing is just mutation. the functional classification according to causation can be useful, and for a while it was thought was the real key.

If you know like RAS is a molecule that really is involved in a pathway that takes signals outside a cell, like wounding or something, and it tells the cell, oh, you better divide because we need to cover up that scrape or fix that cut or whatever. But if something happens and that pathway gets locked on, you know, so the doorbell's ringing all the time, you know, the cells just keep dividing.

If you know like RAS is a molecule that really is involved in a pathway that takes signals outside a cell, like wounding or something, and it tells the cell, oh, you better divide because we need to cover up that scrape or fix that cut or whatever. But if something happens and that pathway gets locked on, you know, so the doorbell's ringing all the time, you know, the cells just keep dividing.

And the idea was, well, if we could inhibit that pathway, then we cured cancer, right? So this was all the excitement around the early 2000s, 2010 to about 2015 was most of these enzymes that do these things are tyrosine kinases or forms thereof. And so that is, you can just inhibit that enzyme, you can cure the cancer by attacking the cause.

And the idea was, well, if we could inhibit that pathway, then we cured cancer, right? So this was all the excitement around the early 2000s, 2010 to about 2015 was most of these enzymes that do these things are tyrosine kinases or forms thereof. And so that is, you can just inhibit that enzyme, you can cure the cancer by attacking the cause.

Turns out, good idea, way too simple because the pathways always have multiple steps. And you can fix one of them, but then if there's another mutation downstream, you're back to where you started and your drug does nothing. And so that's what the problem is because tumors, as they progress, as the tumors become more and more

Turns out, good idea, way too simple because the pathways always have multiple steps. And you can fix one of them, but then if there's another mutation downstream, you're back to where you started and your drug does nothing. And so that's what the problem is because tumors, as they progress, as the tumors become more and more

strange as they start, they become unstable and the genome actually becomes very unstable. And they start, you start getting a lot of more mutations. And as soon as that happens, you have more drivers they're called. And so you can take one out. It doesn't make any difference. You could cure 99%, kill 99% of the tumor cells.

strange as they start, they become unstable and the genome actually becomes very unstable. And they start, you start getting a lot of more mutations. And as soon as that happens, you have more drivers they're called. And so you can take one out. It doesn't make any difference. You could cure 99%, kill 99% of the tumor cells.

It doesn't make any difference because 1% or 0.1% will have another driver and they'll inevitably grow out.

It doesn't make any difference because 1% or 0.1% will have another driver and they'll inevitably grow out.