Apologies for the short post but I’m fighting off what I think is becoming a migraine. However, I just wanted to put up two links to a topic that I covered a fair bit at my old blog home: targeting the aerobic glycolysis pathway of tumor cells, the so-called Warburg effect.
An article in today’s New York Times by Andrew Pollack, “Fuel Lines of Tumors are a New Target,” gives a nice overview of the state of the science in this area, although the article’s title is way off-base as this work has been going on for decades (I realize that writers usually have no control over the titles given to their work). In addition to discussing approaches by drug companies, Pollack cites the work of Chi Dang at Johns Hopkins, Michael Pollack at McGill (no relation, I assume), and Evangelos Michelakis at Alberta.
Michelakis may ring a bell to you because his team has popularized the study of the small molecule, dichloroacetate (DCA), in experimental cancer therapy. Promising animal studies gave rise to a rash of internet marketers of the easy-to-make chemical even before clinical trials were initiated. Michelakis recently published some very limited but promising clinical results but DCA is far from being a cancer treatment. For example, an in vitro and animal study published this month in Cancer Letters revealed that some types of human colon carcinoma cells are actually protected by DCA when grown under anoxic conditions or as xenografts in mice (h/t Scott Gavura). This study highlights the need to fully understand the mechanisms of action of an agent before it goes into clinical trials.
Academic investigators and companies have been looking to target the aberrant energy metabolism of tumors for some time. One interesting drug is L-asparaginase, an enzyme designed to hydrolyze asparagine, an amino acid thought to be preferentially required by some types of leukemia. Even earlier was the alkylating agent, phenylalanine mustard or melphalan, developed to exploit the increased requirement for phenylalanine by some tumor cells (it gets taken up by the valine transporter instead).
Targeting the Warburg effect is promising because it could have greater impact on more than just one type of cancer. However, most drugs to date require extremely high concentrations that are difficult to achieve for sustained periods in people. Nevertheless, it remains an active area of investigation. Pollack’s article attests to that continuing interest, but it closes with a caution from Michelakis about DCA:
“We have only assumptions and theoretical excitement,” Dr. Michelakis said. Still, he added, “there’s no question that this is a new direction that is logical and very appealing.”