Overcoming therapeutic resistance that inevitably develops is one of the major challenges in treating lung cancer. Non-small cell lung cancers that harbor mutations in the epidermal growth factor receptor (EGFR) are initially responsive to targeted therapies known as EGFR tyrosine kinase inhibitors (TKIs). However, most patients eventually develop resistance to these therapies.
One such targeted therapy, afatinib, inhibits not only EGFR but also HER2 (human epidermal growth factor receptor 2, which is overexpressed in aggressive breast cancers). William Pao, M.D., Ph.D., Cornelius Abernathy Craig Chair, and colleagues investigated the potential role of HER2 in cells harboring EGFR mutations.
They report in the journal Cancer Discovery that HER2 was amplified in 12 percent of tumors with acquired resistance to targeted therapies. They showed that HER2 overexpression in cell lines conferred resistance (and HER2 inhibition conferred sensitivity) to EGFR-TKIs. The results identify a previously unrecognized resistance mechanism and suggest that assessing HER2 status – and possibly targeting HER2 – may be beneficial in treating resistant lung cancers.
The research was supported by grants from the National Cancer Institute (CA121210, CA129243, CA068485) of the National Institutes of Health and from Stand Up To Cancer.
