Cancer Breakthrough Aids One Patient, Raises Hopes for Many Researchers use a woman’s immune cells for new therapy to reverse her metastatic colon cancerBy Thomas M. Burton

http://www.wsj.com/articles/cancer-breakthrough-aids-one-patient-raises-hopes-for-many-1481148000

BETHESDA, Md.—National Cancer Institute researchers have produced an immune-cell therapy that for the first time successfully targeted a genetic mutation involved in causing tens of thousands of gastrointestinal cancers.

The research, published in the New England Journal of Medicine on Wednesday, focused on only one patient whose metastatic colon cancer was completely reversed. But that patient’s unusual story may hold promise for many others, doctors said. The therapy targets a gene mutation estimated to drive more than 50,000 new cases of GI cancers in the U.S. each year, including about 90% of often-lethal pancreatic cancers and 45% of all colorectal cancers.

The NCI laboratory is headed by famed immune-therapy researcher Steven A. Rosenberg, the chief of surgery at the cancer institute. He has previously published landmark findings showing that immune therapy has effectively treated many patients with metastatic melanoma, as well as those with blood cancers such as leukemia and lymphoma. The technique also proved successful in a bile-duct cancer case reported in 2014. NCI is part of the National Institutes of Health, which is based here.

Targeting the commonly-occurring family of cancer-driving genes known collectively as RAS has been a kind of Holy Grail in oncology. Mutations in the subset of RAS genes known as KRAS are believed to be a driving force in most pancreatic cancers, which have a bleak survival rate, and in nearly half of colorectal cancers, the No. 2 cancer killer in the U.S. after lung cancer. In this case, the targeted mutated gene is known as KRAS G12D and is the most common of the KRAS gene mutations.

“We report the regression of metastatic colon cancer,” wrote the researchers, headed by Dr. Rosenberg and postdoctoral fellow Dr. Eric Tran. The researchers calculated that tens of thousands of patients annually could potentially be eligible for this treatment.

Dr. Rosenberg said that while the therapy depends on each patient’s own immune cells, it is potentially transferrable to many other patients because of receptors in the patient’s immune cells that grab onto the cancer. These anti-KRAS receptors can be widely used as a treatment, he said.

“This is truly exciting,” said Axel Grothey, a Mayo Clinic oncologist. “At this point in time I consider the presented data as an intriguing proof of principle that cellular immune therapy can be used to target cancer cells with specific molecular alterations. That alone is important and could represent a game-changer in the future.”

“This is really important,” said Leonard Saltz, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York. “It isn’t changing treatment today, but it may change it tomorrow.” He expressed caution because this is just one case, but said, “This is a terrific translation of elegant science into a real benefit for this patient, so in that respect it’s very exciting.” CONTINUE AT SITE

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