Discussion with a Cancer Surgeon

This weekend, I had the opportunity to sit down with a friend, a cancer surgeon who works at a major teaching hospital in the US. He, his wife and two kids were up visiting us for the weekend.

Over coffee, I was asking him about the state of cancer therapeutics. Although he himself does not administer drugs or design treatments, he is part of a larger team which includes molecular oncologists that perform this task. What I heard was quite surprising.

From the vantage point of academia, we have been told that the development of new anti-cancer chemotherapy has been a disaster (here's one example). Every good idea that we've come up with, such as rapamycin, has basically failed in big clinical trials. But according to my friend the view from the bedside is not so bad. For kidney, bladder, and prostate cancer (that was his area of expertise) many of these new drugs ARE being used. None of them is the answer, "each is about 30 to 40 percent effective, there is no silver bullet." However in combination they can actually do a lot of good for treating cancers that are unresponsive to the standard chemo treatments. The list of drugs being used includes rapamycin, anti-tyrosine kinase inhibitors such as Sorafenib, and the anti angiogenesis drug avastin, a compound that came out of Judah Folkman's research. Recently we've learned that new anti-TOR pathway drugs are being developed that not only target the mTORC1 complex, which sits at the center of the TOR pathway, but also the mTORC2 complex, which is related to the first complex except that is unresponsive to rapamycin.

So perhaps all this money being spent at the NIH was worth it ...

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Since TORC2 inhibitors will be likely upstream of TORC1 (via akt), these compounds would seem to act as pan-TOR inhibitors. It just seems like inhibiting all these TORC2 targets (Akt, PKC, SGK, S6K et al) is asking for side effects. This is even outside of the normal side effects for most ATP competitive kinase inhibitors since so many kinases look so similar. I'd love to be proven wrong though, I'm just skeptical of this approach.

By Dave Bridges (not verified) on 19 Oct 2009 #permalink

My understanding is that the overactivation of Akt in response to Rapamycin treatment was part of the problem with using this drug to treat cancer. This feedback loop can now be turned off if you inhibit mTORC2. We'll just have to see what are the consequences of this double-punch.

I do not have the technical knowledge about Oncology. One of my relatives is suffering from breast cancer metastasis. She is undergoing Chemotherapy. What are the treatment options for liver metastasis. Sugery and chemoembolization cant be performed. Do you have any advice?


I am only a basic researcher. Although I know quite a bit about the fundamentals, and about how these different chemotherapeutic treatments affect core biological processes, my knowledge becomes shaky about how this translates upto the level of a patient. Our best knowledge comes from empirical data - what has worked best in the past. A good molecular oncologist should be on top of the latest findings from clinical studies.

My best advice is to ask an oncologist. The effectiveness of any one treatment is highly dependent on the exact type of cancer, the stage it is at and a whole host of other parameters, some of which we are totally ignorant.