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KRAS in its Sights

For one patient, researchers have successfully used T-cell transfer therapy to target mutant KRAS, the New York Times reports.

In a case report appearing this week in the New England Journal of Medicine, a National Cancer Institute-led team describes treating a 50-year-old woman with metastatic colorectal cancer with cytotoxic T cells targeting mutant KRAS G12D. Forty days after treatment, they found that all seven of the patients' tumors had regressed, based on a CT scan, and nine months after that, six of the tumors exhibited continued or complete regression.

The researchers resected the seventh, non-responding tumor and through their whole-exome and transcriptome sequencing analysis found that though it still expressed the KRAS G12D mutation, the tumor had acquired new mutations, including loss of heterozygosity of the region encoding HLA-C*08:02 that likely enabled it to get around the treatment.

The University of Pennsylvania's Carl June tells the Times that this is an important study, as KRAS is a common cancer mutation that has been considered 'undruggable.' However, he notes that the next step is to figure out whether this was "one in a million, or something that can be replicated and built upon?"