Although patients with lung cancer who are treated with the drug erlotinib (Tarceva) often experience an initial decrease in tumor size, those receiving erlotinib also regularly face cancer recurrence.
A team of researchers at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center recently discovered that a human protein, AXL, drives resistance to erlotinib. These study results suggest that blocking AXL may prevent resistance to the cancer drug.
In the experiments, described this week in Nature Genetics, Trever Bivona, MD, PhD, an assistant professor of hematology and oncology, and his colleagues used an inhibitor of AXL that is not an ideal clinical drug. So, Bivona and his team are now collaborating with Kevan Shokat, PhD, a Howard Hughes Medical Institute investigator and chair of the UCSF Department of Cellular and Molecular Pharmacology, to develop more effective AXL inhibitors for clinical testing.
Erlotinib is a targeted therapy that works by blocking an enzyme called epidermal growth factor receptor (EGFR). Bivona and his colleagues discovered that AXL drives resistance to erlotinib by “rescuing” lung cancers from EGFR inhibitor treatment.
“If we block AXL activation in the laboratory, we can overcome resistance to Tarceva,” said Bivona. “This paves the way for novel and more effective therapies.”
Source: UCSF.