Potential new treatment for drug-resistant skin cancer

More than fifty percent of metastatic basal cell carcinomas are already resistant to currently approved drug treatments at time of diagnosis.  These basal cells show no signs of known resistance-associated genetic mutations. This leaves researchers wondering how the cells manage to evade treatment. Now, though, there maybe a new treatment for drug-resistant skin cancer

Anthony Oro, MD, PhD and Ramon Whitson, PhD from Stanford University School of Medicine published a paper on Feb. 5, 2018 in the journal Nature Medicine describing their research.

Most common cancer in US

With approximately 2 million new cases annually, basal cell carcinoma is  the most common cancer in the US. Most of these cancers are successfully treated with surgery, and rarely metastasize. When these cells do metastasize they can be deadly. Skin cancer will affect up to 30 percent of people in the US at some point in their lives.

Understanding the link

The researchers think they have found a link between a cancer cell’s internal scaffolding and the cellular signaling that drives cell growth and allows it to evade the effects of drugs currently approved without genetic mutations.

In 2011, the FDA  approved the use of an inhibitor called vismodegib, as a treatment for basal cell carcinoma. About half of patients treated will respond to vismodegib, but about 20 percent of these will eventually  develop resistance to the drug. The researchers wanted to know why. “We sequenced the heck out of these tumors…” said Oro, one of the researchers. Interestingly, changes in a cancer cell’s shape often enhance its ability to invade surrounding tissues and can lead to metastasis throughout the body.

In previous work Oro’s lab has identified several mutations that occur that cause certain proteins to remain active even in the presence of vismodegib. According to Whitson, “This is the first time anyone has identified the molecular causes behind this link.”

You can learn more about this research in the journal Nature Medicine.

You can read about this research in the Stanford Medicine News Center.