Precision Medicine in the Treatment of Cancer

Study of the biology of squamous cell lung carcinoma leads a team of scientists to conclude that potential new cancer treatment approaches should focus on genetic aberrations rather than on the organ of origin.

New research from scientists at Washington University in St. Louis posits that cancers may be more appropriately classified by their genetics rather than by the primary organ they affect.

“It’s really less about what type of tissue the tumor arises in—lung, breast, skin, prostate—and more about what genes and pathways are affected,” noted Richard K. Wilson, PhD, director of The Genome Institute at Washington University.

Investigators came to this conclusion after examining the normal tissue and tumors of 178 lung squamous cell carcinoma patients. They noticed that the patients had approximately 18 recurring genes in common, and almost all of the tumors displayed mutations in the TP53 gene, a gene thought to help with DNA repair. They also observed that inactivation of the CDKN2A gene occurred in 72% of tumors. Lastly, they identified mutations in the HLA-A gene in the tumors. HLA-A alerts the immune system of trouble by helping to detect foreign polypeptides.

“The old way of doing clinical trials where patients are only tied together by the organ where their cancer originated, those days are passing,” said Mace Rotherberg, MD, senior vice president of Pfizer oncology, to The New York Times.

The study was done through the National Institute of Health’s The Cancer Genome Atlas (TCGA) project and will appear in print in the September 27, 2012 issue of the journal Nature. So far, The Cancer Genome Atlas Research Network has published analyses on glioblastoma multiforme, ovarian serous adenocarcinoma, and colorectal adenocarcinoma.

According to a press release from TCGA, the whole genome data will be freely available for future in-depth research. Scientists hope that making this information easily accessible could help others locate mutations in intergenic regions, which are stretches of DNA sequences located between clusters of genes that may not encode proteins but sometimes control nearby genes.

The study’s findings have enormous implications for the way most cancers are treated. Rather than being assigned a drug that has been created or even tested for a particular type of cancer (breast, lung, prostate, etc), it may be more practical to match the genetic abnormality to a drug that targets one or more of these gene mutations.

Through the identification of the most common gene mutations in adenocarcinoma, investigators also discovered that the drugs needed to treat this disease are either already in use for other cancers, or are currently being tested in clinical trials. TCGA hopes that publishing their research online through an accessible database will help move the discovery of cancer treatments along at a more accelerated pace.

“These TCGA findings should stimulate a wide variety of new clinical trials for patients with squamous cell lung cancer and specific genotypic alterations,” said Matthew Meyerson, MD, PhD, of the Dana-Farber Cancer Institute, the Broad Institute, and Harvard Medical School, and co-leader of the project within TCGA. “These will include clinical trials of PI3 kinase inhibitors and other tyrosine kinase inhibitors, as well as ways to use genomics to select patients for trials of lung cancer treatments that dial down the immune response.”