Newswise — Today, for the first time, a drug has been FDA-approved for cancer based on disease genetics rather than type. Developed from 30 years of basic research at Johns Hopkins and its Bloomberg~Kimmel Institute, pembroluzimab now can be used for colon, pancreatic, stomach, ovarian and other cancers if genetic testing reveals defects in so-called mismatch repair genes.
Experts at the Bloomberg~Kimmel Institute designed the first clinical trial to test the theory that patients whose tumors have defects in mismatch repair genes may respond better to immunotherapy. Results of the trial, which were funded primarily by philanthropic foundations including the Lustgarten Foundation, the Ludwig Institute, the Howard Hughes Medical Institute, the Commonwealth Foundation, and Swim Across America, were presented and published in 2015 at the American Society of Clinical Oncology Annual Meeting and published online by The New England Journal of Medicine.
Tests for defects in mismatch repair are widely available, costing $300 - $600. Pembrolizumab can cost approximately $100,000 per year, fueling the need to identify patients who are likely to respond to the drug.
First identified in 1993 by scientists at Johns Hopkins and other institutions, mistakes in mismatch repair genes occur in more than 4 percent of cancers that occur each year in the U.S., including colon, uterus, stomach, gall bladder, pancreas, ovarian, prostate and small intestine. The mutations disable cells’ ability to repair errors in the DNA replication process, which triggers unchecked cellular growth, a hallmark of cancer.
Two decades later, an idea took root when Johns Hopkins experts found mismatch repair defects in a single patient with colon cancer who responded to immunotherapy while other patients with colon cancer did not.
Patients with tumors laden with mismatch repair defects have an abundance of abnormal proteins that look more “foreign” to immune system cells, triggering them to search for and destroy the unfamiliar-looking cancer cells.
Experts available for interviews to discuss the approval’s significance and its potential impact among patients with cancer include:
Dung Le, M.D., oncologist at the Johns Hopkins Bloomberg~Kimmel Institute, and leader of the clinical trial of mismatch repair defects and pembrolizumab.
Drew Pardoll, M.D., Ph.D., director of the Johns Hopkins Bloomberg~Kimmel Institute. Pardoll helped design the pembrolizumab clinical trial.
Bert Vogelstein, M.D., co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and a member of the Bloomberg~Kimmel Institute. Vogelstein linked mismatch repair defects to cancer in 1993 and helped develop the idea for the clinical trial.