Promising new drug flags evasive cancer cells for destruction

UCSF researchers have developed a new tool to fight a common type of cancer. The therapy combines a targeted drug that blocks mutated, cancer-causing KRAS proteins—found in one quarter of cancerous tumors—with immunotherapy that eliminates tumor cells altogether.

While some drugs that target KRAS can shrink tumors, the approach isn’t always a permanent fix, and many cancers eventually resume their pernicious growth. Building on this approach, Charles Craik, PhD, faculty member in the UCSF School of Pharmacy’s Department of Pharmaceutical Chemistry, and Kevan Shokat, PhD, faculty member in the School of Medicine, have found a promising way to defeat these drug-resistant cancers resulting from mutated KRAS.

In the study, published on September 12 in Cancer Cell, Craik and his team showed that ARS1620, a type of KRAS inhibitor, does more than block KRAS—the drug also makes KRAS visible to the immune system. “This mutated protein is usually flying under the radar because it’s so similar to the healthy protein,” says Craik. “But when you attach this drug to it, it gets spotted right away.”

Sensing an opportunity, the team then designed an immunotherapy to recognize cells bearing these exposed proteins and recruit the immune system’s T cells. Tests on human cells in the lab showed that the immunotherapy could kill tumor cells with mutated KRAS that were treated with ARS1620, including those that had already developed resistance to the drug.

Craik believes that this two-pronged approach could be used to go after other cancer targets.

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Drug Turns Cancer Gene Into ‘Eat Me’ Flag for Immune System (UCSF News)