Major Development Could Further Advance Personalized Cancer Therapy

Researchers from Georgetown Lombardi Comprehensive Cancer Center (Washington DC, USA) reported a significant advance in this field of research using a new chip that hunts for hundreds of mutations in dozen of genes.

The goal of personalized medicine is to determine the best treatment and the optimal dose carrying the fewest side effects, particularly as new drugs are discovered and treatment options increase. Variations in an individual's genes encode proteins, which affect how a drug is metabolized or taken in by the cells. This directly influences the drug's effectiveness and the kinds of side effects that may be caused by its toxicity.

"Currently, available genotyping tools test only a few genes at a time,” explained Dr. John F. Deeken, a pharmacogentic researcher at Lombardi. "With a new chip called DMET, as many as 170 genes can be examined for more than a thousand variations. This type of turnkey testing, if validated, could eventually replace highly specialized, time-consuming, and labor-intensive testing--thus allowing more institutes the opportunity to pursue genotyping and pharmocogenetic research. That alone would be a significant development for our field and for expediting the research many of us believe is the future of medicine.”

Such a development is especially critical for cancer research, both in terms of drug discovery and treatment. Genetic variability among patients in cancer clinical trials is not typically taken into account, a factor that could skew dosage amounts and doom an otherwise promising new drug. A simpler and faster test could be readily integrated into treatment trials.

In his article published online December 29, 2009, in The Pharmacogenomics Journal, Dr. Deeken and colleagues reported results of the new genotyping platform called DMET (drug-metabolizing enzymes and transporters), developed by Affymetrix, Inc. (Santa Clara, CA, USA). The DMET "casts a wider net,” screening for 1256 genetic variations in 170 genes involved in drug absorption, distribution, metabolism, and excretion.

According to Dr. Deeken, one of the main obstacles facing pharmocogenetic researchers is the lack of a proven and relatively quick technology for genotyping. "DMET appears to offer great promise in this field as a reliable test unveiling genetic variations that correlated with drug effectiveness and toxicity,” stated Dr. Deeken. "Still, DMET isn't yet ready for primetime in terms of having received FDA [U.S. Food and Drug Administration] approval, but we're getting closer.”

Dr. Deeken serves as a consultant to Sanofi-Aventis (Bridgewater, NJ, USA), the manufacturer of docetaxel, a drug involved in the study.

Related Links:
Georgetown Lombardi Comprehensive Cancer Center
Affymetrix