Former president Jimmy Carter no longer needs treatment for the metastatic melanoma that spread to both his liver and brain. His miraculous recovery is thanks to a drug called Keytruda, one of a group of new drugs that centers on treatment called immunotherapy.
These drugs use an individual’s own immune system to fight off cancer—in Carter’s case, melanoma, which kills an estimated 10,000 Americans each year. Keytruda is a treatment that some have referred to as the “golden age of chemotherapy drugs” and a “miracle cure.”
But how exactly does it work?
Chemically known as pembrolizumab, Keytruda was introduced in 2014 at the American Society of Clinical Oncology conference in Chicago. In a room too packed for seats, a team of Israeli and American scientists explained the secret to the drug’s success: the PD-1 pathway.
Normally when an infection occurs in the body, certain cells alert the immune system. The immune system then activates what are called T-cells. The “soldiers” of the immune system, T-cells locate the intruder and kill it off. Cancer, however, disrupts this model using a PD-1 pathway.
Short for “programmed cell death protein 1,” PD-1 is a protein that functions as an immune checkpoint. In order to evade being attacked and destroyed, cancer cells take over the PD-1 pathway—in turn, preventing the activation of T-cells.
Keytruda and other immunotherapy drugs block the PD-1 pathway. Without it, the cancer is visible to the T-cells, and it loses the ability to multiply undetected. “This medicine is a miracle cure—it’s a real breakthrough,” said Dr. Jacob Schachter, one of the Israeli researchers.
Following the presentation, the Federal Drug Administration granted Keytruda’s maker, Merck, a “breakthrough therapy” designation, a way to fast-track drugs for life-threatening conditions. In the months following, the FDA fast-tracked it for other cancers, including colorectal and lung.
Given Carter’s miraculous recovery from a deadly cancer, the drug deserves all the credit it’s getting. But the Merck team stood on the shoulders of another group of scientists—one that, the same year, was awarded the top scientific prize from the Cancer Research Institute. The team discovered the PD-1 pathway.
“The discovery of PD-1 as a new immune checkpoint that can be exploited in cancer immunotherapy was a triumph of scientific collaboration, made possible by a continuum of research spanning more than a decade,” Dr. Jill O’Donnell-Tormey, director of scientific affairs at CRI, said. “With PD-1 checkpoint inhibitors added to the therapeutic arsenal of combination therapies, we hope to see even bigger responses in more patients.”
While immune checkpoint inhibitors had been explored as a means of treating cancer, scientists had yet to discover the disease’s ability to “hijack” the PD-1 pathway and render T-cells inactive. CRI called the work “groundbreaking,” a discovery capable of “revolutionizing cancer therapy today.”
Scientists at the Dana-Farber Cancer Research Institute expanded on the concept in a paper published in Paths of Progress last May. “This is a story about the velocity of an idea,” the essay begins. “A discovery whose potential to improve cancer treatment practically leapt from the test tube.”
The paper explains Dana Farber’s early work on the PD-1 pathway in 2001, which the authors call “an elaborate masquerade” that allows cancer cells to “live and multiply without harassment from the immune system.” The first clinical test of a drug that would inhibit the pathway began in 2008. According to the authors, more than 12 have been completed and dozens more are in the works.
Beyond just a big discovery, the paper paints the discovery as a pivotal to curing cancer. “More than a century after scientists recognized the immune system’s potential as a cancer warrior, immunotherapy is rapidly becoming a mainstay of the anti-cancer arsenal.”
If ever there was a time for a breakthrough in the cancer world, it’s now.
An estimated 39.6 percent of men and women worldwide will be diagnosed with cancer at some point in their lifetime, making it one of the leading causes of death. According to the American Cancer Society, at least 1.6 million people will be diagnosed with cancer in the U.S. this year, and an estimated 595,690 will die from the disease.
With statistics this grim, it’s no wonder that Carter’s initial announcement of his cancer diagnosis last year came with the suggestion that he’d accepted the idea of dying. “You know, I’ve had a wonderful life,” he told reporters at the Carter Center on Aug. 20. “I have had an exciting and adventurous and gratifying existence.”
While hopeful that his treatment would help, Carter said he was ready to “accept anything that comes.” Several rounds of radiation and doses of Keytruda later, Carter’s message was noticeably more spirited. “The doctors determined that I didn’t need any more treatment,” he said in a video. “So, I’m not going to have any more treatment.”
Carter’s success story shines light on a drug that may be the best defense against cancer we’ve seen yet.