December 13, 2017
Chronic stress may promote resistance to lung cancer therapy
BY Clayton Boldt, Ph.D.
Elevated levels of chronic stress hormones, such as those produced by psychological distress, may promote resistance to drugs commonly used to treat lung cancer patients with EGFR mutations, according to new research from MD Andrerson Cancer Center. Retrospective analysis of clinical patient data suggests that beta blockers may slow or prevent the development of resistance to EGFR inhibitors.
The research, published today in Science Translational Medicine, used non-small cell lung cancer (NSCLC) cell lines and mouse models to discover and validate the pathway by which stress hormones drive resistance to these therapies, known as EGFR tyrosine kinase inhibitors (TKIs).
Approximately 160,000 people in the U.S. are diagnosed with NSCLC each year, and roughly 15,000 have metastatic disease with EGFR mutations, meaning they could benefit from targeted EGFR inhibitors.
For these patients, EGFR inhibitors initially work well, but resistance inevitably develops, explained John V. Heymach, M.D., Ph.D., chair of Thoracic/Head and Neck Medical Oncology. This resistance is sometimes associated with another EGFR mutation, called T790M, but in other cases the cause is not well understood.
“It is generally accepted that stress is not good for cancer patients, but a cancer diagnosis as well as the necessary treatments can be quite stressful. This data indicates that stress hormones may act directly on tumor cells and promote resistance to therapy,” said Heymach, the study’s senior author. “The concept that beta blockers, which are well-tolerated and inexpensive, may improve responses to EGFR targeting agents is exciting and should be tested clinically."
Researchers had previously identified a connection between EGFR inhibitor resistance and the immune signaling protein IL-6, which is activated by stress hormones. Therefore, the researchers sought to investigate stress hormone signaling as an alternative mechanism driving resistance to EGFR targeted therapies.
Read more about the study in the MD Anderson Newsroom.