David Scadden: Where is often been viewed as a disorder of genetic disruption of a particular cell type that goes on to have an unlimited growth and invasion capabilities and then metastasize. Now we’ve often focused on the cancer cell as something that is an entity that it is distinctive from the rest of biology. It has this disordered genetic information by virtue of mutations. And it develops some amount of heterogeneity, some cells are not, they start identically but then they start to change and it’s generally been thought that the cancer has a fairly equivalent composition. That is that all the cells, they may look a little different but they’re all pretty much the same nasty creature.
And one of the things that has happened by virtue of viewing cancer through the stem cell lens, is that there is some sense that maybe cancer, like normal tissue, is organized so that there’s a hierarchy of cells, if you will. And at the base of this hierarchy is a very primitive cell type, a stem cell or a stem cell like cell, and it gives rise to all the other cells of a normal tissue or of a malignant tissue. And that it’s among the number of cells that composes tissue relatively modest and negative.
So for example in our blood system, we have a very very tiny number of stem cells that gives yield to tens of millions, tens of billions, a thousand billion new blood cells a day. So that capacity to generate offspring is something that, maybe that’s what a cancer stem cell does. And yet all of those blood cells that are generated from a normal stem cell actually tend to die out. What happens if that’s true in cancer? Maybe there’s just a few cells that are really essentially the root of the cancer. The stem cell, they are capable of self renewing, capable of forming metastasis, and that those are the root cause of cancer.
And while we develop drugs generally by trying to target the bulk of the tumor, maybe what we’re doing is actually missing the opportunity to cure the tumor because we’re not focusing on those root causes of the stem cells. And that model has been around for a long time, it’s just recently been tested. And it was demonstrated to actually be true in human leukemias. Now, whether this is true in other cancer types in humans, is something that there’s evidence on both sides of this debate. But certainly I think for some tumors that model will be useful and it will change the way we do drug development. We’ll focus more on trying to eliminate the cancer stem cell, or the equivalent of, and maybe even try to not just target the suspect but follow them and see how we’re doing. If we’re just following the bulk of the tumor, what can happen is we can see remissions but perhaps not cures. Our hope is that if you focus on the root cause of the stem cell you’d be able to generate cures.
Recorded on: July 06, 2009