Over the last decade or so, treatment advances have added a full year to the median survival of patients with metastatic colon cancer. Much of the credit goes to a new class of drugs called EGFR (epidermal growth factor receptor) inhibitors. They block EGFR, a cell-surface receptor that fuels cell growth and proliferation and is abundantly present on the surface of colon cancer cells (and is found in other types of cancer as well).
Unfortunately, a large percentage of patients with colon cancer do not respond to EGFR inhibitors. The cancer's response to these drugs depends on a gene called K-ras: tumors with a mutated form of K-ras are drug resistant. But something else must also be counteracting these drugs.
"Even if you exclude colon cancer patients with mutant K-ras genes, you still find that only about half of colon cancers respond to EGFR inhibitors," says Sanjay Goel, M.D., M.S., associate professor of medicine (oncology) at Einstein and attending physician in oncology at Montefiore Medical Center. In laboratory studies of colon cancer cells from 22 patients, Dr. Goel and his colleagues discovered two other genetic anomalies—mutations to the genes PIK3CA and PTEN—that reduce a tumor's sensitivity to EGFR inhibitors.
Moving from the lab to a study of 76 patients with colon cancer, the researchers found that the presence of the two mutations reliably predicts a poor response to EGFR inhibitors, as they reported last year in Clinical Colorectal Cancer. Einstein and Montefiore have since filed and received a patent on the use of PIK3CA mutations to predict whether or not patients will benefit from EGFR inhibitors. The patent has been licensed for development by Transgenomic, Inc., an Omaha, NE, biotechnology company.
The PIK3CA/PTEN test could spare a fair number of patients treatments that will not help them. "EGFR inhibitors can be quite toxic, with side effects ranging from skin rashes to diarrhea," says Dr. Goel. The test would also reduce healthcare expenditures, he notes, since taking these drugs can cost thousands of dollars a month.
Posted on: Friday, December 13, 2013