Sunday, August 29, 2010

Guided evolution in cancer therapy

Another of my speculation is cheap (but fun) posts.

I searched Google Scholar today with the terms guided evolution cancer. I didn't find anything interesting. I bet, however, that in 10 years a similar search will have many hits. Today, for example, a search on guided evolution HIV gets some tantalizing hits.

The idea is easier to understand in the context of HIV, particularly if you know the evolutionary history of  parasite/prey relationships. So I'll start with predator/prey, then HIV, then Cancer.

When a pathogen, like the rabies virus or smallpox, is introduced to a new species it is often very lethal. Over time it often transitions from parasite to symbiote. This transition involves adaptation by both host and parasite. This happens because one of the best ways to "get ahead" in the living universe is to "get along" -- particularly if your host shows "promise".

HIV (and other retroviruses) have such mutable genomes that they evolve within the lifespan of a human host. Modern HIV therapy takes advantage of that. Therapy tries to trap the virus into an adaptation box, where one adaptation compromises another. I wouldn't be surprised if the newest therapies try to guide HIV to evolve down a path where a yet-to-be-used drug will be particularly potent. That would be guided evolution in an HIV context.

Which brings me to cancer. All physicians know patients who have lived many years with a metastatic cancer. The malignancy is not gone, but neither does it kill. The host and the "parasite" are "getting along. In time the tumor will kill, but of course we all die. The goal of medicine is not (yet) immortality, but rather deferred morbidity.

If we think of a cancer as a competing set of "parasites" (for the cancer is genetically diverse) laying claim upon the resources of the host, then can we guide the evolution of that ecosystem? Could we use one set of drugs to guide the development of a subset of the cancer that will outcompete other tumor lines? That successful subset might be so guided as to be very vulnerable to a "knockout" drug -- or to persist but in a relatively tame state.

Just speculation. I'm only about 50% right with these sorts of things.

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