February 10, 2016

Overcoming lung cancer drug resistance

Vanderbilt investigators have discovered a way to overcome the resistance of some lung cancers to certain targeted therapies, which could lead to more effective treatments for lung cancer patients.

Despite advances in diagnosis and treatment, lung cancer is the leading cause of cancer-related death. Many lung cancer patients have mutations in the proteins regulating cell growth, such as the epidermal growth factor receptor (EGFR).

Tumors with EGFR mutations are initially extremely responsive to EGFR-specific tyrosine kinase inhibitors (TKIs). Unfortunately, tumors rapidly become resistant to TKIs and begin to bypass inactivated EGFR, rendering these drugs ineffective.

Last month in Cancer Research, Katherine Amato, Ph.D., Jin Chen, M.D., Ph.D., and colleagues reported the identification of a signaling protein, EPHA2, which is overexpressed in EGFR TKI-resistant lung cancer cells.

These drug-resistant lung cancer cells were remarkably sensitive to EPHA2 blockage by a small molecule inhibitor, which decreased viability of cells with acquired resistance to a third generation TKI. This suggests a potential method to overcome EGFR TKI resistance, and ultimately may lead to more effective treatments for lung cancer patients.

This study was supported in part by National Institutes of Health grants CA950004, CA177681, CA173469, CA121210, CA129243, CA143798 and CA167878.

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