Over half of newly diagnosed advanced or metastatic basal cell carcinomas are resistant to currently approved drug treatments. Yet many of these skin cancers harbor no known resistance-associated genetic mutations, leaving researchers and clinicians wondering how they manage to evade treatment.

Now, researchers at the Stanford University School of Medicine have identified a link between changes in the cancer cells’ internal scaffolding and one of the last steps of the cellular signaling pathway that drives their growth. This previously unknown connection allows the cells to neatly sidestep the effects of currently approved drugs without requiring them to acquire specific genetic mutations.

The researchers found that blocking this connection using an inhibitor previously used to treat inflammation significantly slowed the growth of drug-resistant basal cell carcinomas in mice. Moreover, human primary tumors grown in the lab also responded to the blockade, highlighting the therapeutic potential of this approach.

The findings suggest new ways to tackle the common skin cancer, which affects up to 30% of people in the United States at some point in their lives. It also may help researchers better personalize their treatments by identifying patients most likely to respond to certain drugs.

“Many of these tumors are resistant at the time of their diagnosis,” said professor of dermatology Anthony Oro, MD, PhD. “Our findings support the idea that tumors have a ‘resistance toolbox’ of mechanisms from which they can choose, based on their microenviroment, that doesn’t depend on genetic mutations often associated with the disease.”

A paper describing the research was published online Feb. 5 in Nature Medicine. Oro is the senior author, and postdoctoral scholar Ramon Whitson, PhD, is the lead author.