The US Food and Drug Administration approves the first genetic makeup-based cancer treatment

Cancer is traditionally identified by where in the body it develops. Breast cancer forms in the breast, lung cancer forms in the lungs, and so on. Even when cancer has spread to a different part of the body, it is determined by its original location. If colorectal cancer spreads to the brain, for example, it is called metastatic colorectal cancer, not brain cancer. But many physicians, including Shayma Master Kazmi, MD, RPh, a medical oncologist at our Hospital in Philadelphia, call that old-fashioned thinking. “We used to think of cancers in terms of where they started,” says Dr. Kazmi. “We are now broadening our views on cancer to not limit ourselves to a starting point, but to see its design, the way cancer spreads, the way it grows, and what makes cancer work.”

innovative treatment

The U.S. Food and Drug Administration (FDA) backed this perspective in May, when it took the critical step of approving a cancer treatment based not on a tumor’s primary site, but on a specific genetic feature found in the cancer’s DNA. Approval allows for the checkpoint inhibitor pembrolizumab (Keytruda® .) ^.) for use in treating patients with inoperable metastatic tumors that have one of two specific genetic characteristics, called microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR). These genetic mutations make it difficult for a cell’s DNA to repair itself, which can lead to a type of uncontrolled cell growth that causes many tumors to form and grow. The decision marks the first time in its history that the Food and Drug Administration has approved a cancer treatment based on a genetic trait. “This critically important decision by the Food and Drug Administration (FDA) that changes the paradigm is another example of how to determine future cancer therapies,” says Murray Markman, MD, chief of medicine and science, Cancer Treatment Centers, of America. ^® (CTCA).

Checkpoint inhibitors such as pembrolizumab are immunotherapy drugs designed to disrupt communication, common between some cancer cells and disease-fighting T cells, that allow cancer to hide from the immune system. Immune cells are almost like the body’s police force, in that they check other cells as they pass through certain checkpoints to determine if they pose a threat that must be neutralized, such as infection or disease. But because cancer is made up of non-functioning body cells, some cancer cells can mask their threat by sending tricky signals to protein receptors, which are on the surface of immune cells, as they pass through checkpoints. Checkpoint inhibitors are so named because they work by blocking those receptors and exposing the cancer as harmful and ready to attack. If not for these checkpoints, the immune system could attack healthy cells. The goal of checkpoint inhibitors is to keep healthy cells protected while allowing the immune system to recognize the risk of cancer. But it doesn’t always work as designed, and scientists are still trying to figure out why.

Huge first step

“These drugs put the brakes on the immune system so that our T cells can look for a foreign antigen,” says Dr. Markman. “The question is: What cancer cells are they going to find when they release the brakes? What are they attacking?” Pembrolizumab, for example, produces positive results about 20 percent of the time it is used. While researchers don’t know why it works in some patients and not others, what they have discovered is that defects in MSI-H and/or dMMR are found in cancers where the drug has shown positive results, regardless of where the tumor is. . Located. In fact, these defects are found in different patients, in all types of cancer. MSI-H is detected in 15 percent of all colorectal adenomas, as well as in patients with bladder, breast, prostate, and thyroid cancer.

So far, the U.S. Food and Drug Administration has approved checkpoint inhibitors to treat different types of cancer, but only based on where they form in the body, such as the lung, bladder, and kidneys. The drugs are also approved to treat Hodgkin lymphoma and metastatic melanoma. By adopting this new approval solely on the specific genetic trait of cancer, the FDA is taking the “big first step” in changing how cancer is treated in the future, Dr. Kazemi says. “It’s very exciting that the FDA has been so progressive in changing its views on conventional cancer treatment,” he says. “We don’t want to be constrained by the origin of cancer. We want to attack it at its core, its driving mechanism.”

Learn more about why immunotherapy is effective for some patients but not for others.