CANCER CURE-NOT YET

Hello everybody, John Marshall for Medscape on our video blog series. You all have been great; we're getting lots of good feedback from folks when I started to prod a little bit about what's going on out there in oncology. I wanted to kind of get back to basics today because just the other morning it was my turn, yet again, to teach our fellows about how chemotherapy works. One of the lectures that I give focuses on the inhibition of the thymidylate synthase, or essentially folate metabolism in a cell. Of course, if you're as old as I am, you cut your teeth on this pathway, the concept of 5-FU hitting one part of the pathway, methotrexate hitting another part of the pathway, leucovorin sort of rescuing one, and helping out on the other. If you remember back, what we did so much of when I was first coming on was that we were convinced that if only we could optimize the treatment within this pathway, if we could get the timing right, if we could combine these drugs in just the right way and maybe even bring in some new medicines, that we could shut this thing down and we could cure cancer.

The reality is, we didn't. We failed at doing that, but it's all we had, and it was logical because these were the only toys we had to play with. We put them together in these ways to try to optimize the therapy. The reason that this resonated with me is that I look at meetings today, or at what's being published in abstract form, and what I see is that a whole lot of it is essentially the same thing, that we're hitting the EGFR pathway here, and then we're going to hit it down here. Or we're going to hit the same receptor twice with an antibody and a tyrosine kinase inhibitor. Our belief is that if we could only control this pathway better, if we could only shut down this network of metabolism better, then, in fact, we could cure cancer, and we would really push the bar further.

Now, we all hope that that is indeed true. We hope that what we're going to see is that by combining these medicines in novel ways, we achieve added benefit without added toxicity. We just have to reflect back on our history, though. In the past, we did this because it was all we had. In fact, the medicines really didn't work that well. It turned out that the combinations really didn't solve the problem. Are we just doing the same thing again? Are we reliving a failed history, or are we indeed pioneering forward in the era of targeted therapy? Just a challenging thought this morning to all of us who are doing these combination early-phase clinical trials. Remember back to 5-FU, methotrexate and leucovorin, as we go forward in our new venture. John Marshall for Medscape. Have a good day.