The road from an idea to a useful drug is a long one, and in cancer it is often particularly long. One reason is that to be able to tell whether a given treatment is effective against cancer often takes several years at a minimum, in order to determine if patients receiving the new treatment are surviving their disease longer than those who are not. Surrogate endpoints are usually not enough. Tumor shrinkage in response to a drug often does not correlate with prolongation of survival, although the converse (i.e., lack of tumor shrinkage in response to a new drug) does strongly correlate with failure of a treatment to prolong survival. In other words, effects observed on surrogate endpoints are not enough to judge whether a cancer therapy is working or not.
Three years ago, predating the existence of this blog by nearly a year, I became aware of a story that involved many of the issues in bringing a compound from the laboratory to the clinic. The case was unusual in that is is very rare to see the scientific process by which new drugs progress through the stages of cancer research, from concept to testing in cell culture to testing in animals to testing in humans challenged so strongly by patients themselves. The reason that this normally doesn’t occur is that new cancer treatments are almost always the product of either university-conducted research, pharmaceutical company-conducted research, or partnerships between the two. This case was markedly different in that it involved a chemical that was not only easy to synthesize, but cheap and long out of patent. Even more intriguing, it targeted a metabolic abnormality found in many cancer cells, an abnormality first described nearly 80 years before by Otto Warburg in 1928. This latter aspect of the drug gave it every appearance of a “rediscovery” of old wisdom that big pharma had ignored for 80 years, and that only added to its mystique.
The chemical was dichloroacetate (DCA), and three years ago it created a world-wide sensation. Last week, it created a sensation again, as breathless news reports once again overhyped its promise. Since I’ve been following the story since early 2007, I appear to be in as good a position as anyone to tell the story thus far and put the new findings into context. To begin that process, let’s head back to January 2007.