Human Lymphocyte
Human Lymphocyte
High-resolution microscope image of a lymphocyte, the part of the immune system that interacts with Keytruda [‘T Lymphocyte’ from NIAID]

Results from a small clinical trial comprising 86 cancer patients have prompted scientists to rethink how different cancers are classified and treated.

The drug being assessed was Keytruda, a recent addition to oncologists’ arsenal of cancer immunotherapy drugs.  Unlike traditional chemotherapies, which poison and kill cancer cells directly, cancer immunotherapy recruits the body’s own self-defense machinery to attack tumors.  Although our immune systems are very good at finding and killing things that don’t look anything like us, such as bacteria and parasites, cancer cells are typically more elusive.  In fact, many develop “cloaking” mechanisms that allow them to further evade detection.  Keytruda works by blocking one of these protective mechanisms, allowing the immune system to properly identify and destroy the cancer.

Of the 86 patients in the trial, an astounding 66 saw their tumors either stop growing or start to shrink (18 of which showed complete remission).  What makes these results even more stunning is that all of the patients had an advanced-stage cancer that was unresponsive to other therapies.  Furthermore, their cancers originated from one of twelve different locations in the body—in other words, they collectively had twelve “different” diseases.  What these cancers had in common, however, was a cadre of mutations that hamper the repair of damaged DNA.  As a result, the tumor cells looked very different from normal cells, making them prime targets for immune system-mediated annihilation.

In a first-of-its-kind decision, the FDA has approved Keytruda for the treatment of virtually any tumor that contains these same mutations in its DNA repair system.  Just as most of us distinguish colon cancer from skin cancer, previous approvals had been limited to specific diseases defined by the tissue of origin.  By thinking a little differently about how to classify cancers, up to 60,000 patients annually now have access to a potentially life-saving medicine.

Acknowledgments: Many thanks to Dr. Rose Joachim, a recent graduate of the Biological Sciences in Public Health Ph.D. Program at Harvard University, for providing her expertise and commentary on the topic.

Managing Correspondent: Christopher Gerry

Original Research: Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade – Science

Media Coverage: Cancer Drug Proves to Be Effective Against Multiple Tumors – The New York Times

SITN Coverage: New Directions for Cancer Therapy: Targeted Medicine  

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