Study homes in on ‘exceptional responders’ to cancer drugs

doi:10.1126/science.370.6520.1020

GSTDTAP > 气候变化

DOI	10.1126/science.370.6520.1020
	Study homes in on ‘exceptional responders’ to cancer drugs
	Jocelyn Kaiser
	2020-11-27
发表期刊	Science
出版年	2020
英文摘要	Although even the best cancer drugs don't buy much time for most people with advanced cancer, there are rare exceptions: patients whose tumors melt away and who remain healthy years later. Researchers have long dismissed these “exceptional responders” as unexplainable outliers. Now, an effort to systematically study these unusual patients is yielding data that could help improve cancer treatments. The project, led by the U.S. National Cancer Institute (NCI), examined tumor DNA and the immune cells found around or within the cancers in 111 exceptional responders. In 26 of the patients, scientists found clues that may explain why a drug that didn't work for most people shrank the tumors for months or years. Some cases suggest new drug combinations could yield better outcomes for other patients. The study, published last week in Cancer Cell , “opens new avenues for treating comparable cancers in the wider population,” says Dale Garsed of the Peter MacCallum Cancer Centre in Australia. The former NCI director who launched the project in 2014 is also excited. “It is gratifying to see so much novel information from this initial survey of patients who have done unexpectedly well with existing therapies,” says cancer biologist Harold Varmus of Weill Cornell Medicine. The results are “complex,” he says, but they “promote unique hypotheses” and highlight the value of conducting genomic tests of patients' tumors in order to customize treatments. Varmus was inspired in part by a bladder cancer patient who responded to a generally lackluster drug—an outcome traced to mutations in her tumor. He funded a team led by NCI's Louis Staudt and Percy Ivy, who with Baylor College of Medicine and other academic collaborators combed through some 500 cases, largely cancers that had spread, for those that fit criteria for an exceptional response—such as having tumors shrink or disappear in response to a drug that worked for less than 10% of patients overall. After removing cases that lacked adequate medical data or tumor samples, they ended up with 111 patients. Their tumors went through a battery of genomic analyses and tests for immune cells. In 26 cases, the data appeared to explain the patient's exceptional response. For example, a patient with brain cancer who was still alive after more than 10 years had received a chemotherapy drug called temozolomide that kills tumor cells by damaging their DNA. The patient's tumor had genomic changes that crippled two DNA repair pathways, which cells use to counter the drug's assault. Another patient, in remission from colon cancer for nearly 4 years after temozolomide treatment, also had two disabled DNA repair pathways, and had received a second drug that blocked a third. “Every backup system that would have reversed the damage was inactivated” in this person, Staudt says. These results suggest a cocktail of drugs, blocking different DNA repair pathways, could help some patients, Ivy says. In other cases, tumors shrank after the patients received a drug that blocks a protein driving cell growth. The tumors had DNA changes that spurred activity of the protein's gene, which made the tumor cells highly dependent on the growth signal; as a result, the drug worked unusually well. Still other exceptional responders had tumors that were infiltrated with high levels of certain immune cells. This suggests their immune systems were primed to swoop in and destroy tumors once a cancer drug started to kill some cells, Staudt says. The findings suggest more genomic testing of tumors could improve treatments. But the DNA results may still be hard to interpret. Many cancers had confusing combinations of DNA and immune cell changes, and the evidence wasn't strong enough to draw firm conclusions in 85 of the cases. NCI is putting data for all 111 patients in an online database so that other researchers can study it and look for similar cases. “Maybe we missed something,” Staudt says. Researchers in North America, Europe, and Australia have launched similar exceptional responder projects, and NCI researchers hope some of these efforts can pool their data. Staudt would like to see a study of at least 1000 patients. “These are puzzles to be solved,” he says. “I do think they teach us something.”
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/304854
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jocelyn Kaiser. Study homes in on ‘exceptional responders’ to cancer drugs[J]. Science,2020.
APA	Jocelyn Kaiser.(2020).Study homes in on ‘exceptional responders’ to cancer drugs.Science.
MLA	Jocelyn Kaiser."Study homes in on ‘exceptional responders’ to cancer drugs".Science (2020).