San Diego — Dennis Lyon was a genetic train wreck. Cancer was ravaging his liver, lungs, bones and brain, and tests showed so many tumor mutations that drugs targeting one or two wouldn't do much good. It seemed like very bad news, yet his doctors were encouraged.
The reason: People with the most messed-up genes often are the ones who do best on treatments that enlist the immune system.
"These are the patients we used to be very depressed about," thinking they couldn't be helped, said Dr. Razelle Kurzrock at the University of California, San Diego. "Now when we see those types of patients, we're really excited," because there are so many ways for the immune system to recognize the cancer cells as abnormal.
Immunotherapy is the hottest thing in cancer care. Drugs called checkpoint inhibitors can vanquish some advanced cancers by removing a chemical cloak that hides them from the immune system. Former President Jimmy Carter got one at age 91 for skin cancer that spread to his brain, and now is in remission.
But they're expensive, have side effects, and work for only about one-quarter of patients — as few as 5 percent with colon cancer and as many as half with the skin cancer, melanoma. Sometimes the benefits are brief.
Worst of all: For a small number of unlucky folks, treatment can backfire. Their cancer grows exponentially after getting a checkpoint drug.
"We're going to have to figure out not only who to treat with immunotherapy but who not to treat," Kurzrock said.
The first step is testing for a protein called PD-L1 that's often involved in forming that chemical cloak. Some checkpoint drugs target this or a related protein, so people with a lot of it should respond to treatment.
That was the hope when Diane Tippett showed up last October at Georgetown Lombardi Comprehensive Cancer Center with a salivary gland cancer that had spread to her liver and lungs.
Dr. Louis Weiner, the center’s director, ordered tests that showed Tippett had a PD-L1 mutation, meaning her cancer made a lot of it. He started the 49-year-old Leonardtown, Maryland, woman on a checkpoint drug, Opdivo, and told her to come back in a few months.
Now, Tippett's lung tumors are gone. Her liver tumor shrank 50 percent and is stable. She got married in July and says she feels great.
Max Krummel is working on a roadmap to do that.
The University of California, San Francisco, scientist heads a project with $10 million from three companies that make checkpoint drugs. He is analyzing hundreds of tumor samples to see what immune system features spell success or failure.
"We're not looking at how the immune system changes," but for what starting point works best with the drugs, he said.
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