Lung Cancer in Patients Who Have Never Smoked
One in five individuals who are diagnosed with non-small cell lung cancer have never smoked and the majority are females. Lung cancer in individuals who have never smoked is now ranked the seventh leading cause of cancer death worldwide, with rates continuing to increase. These lung cancers are different in many ways from those that occur in former or current smokers. Most have distinct genetic defects, including mutations in the epidermal growth factor receptor (EGFR) gene. While patients with EGFR-mutated lung tumors respond well to oral medications intially, these tumors eventually escape treatment and continue to grow, leaving few options for subsequent therapy.
A team of oncologists and researchers at Fox Chase Cancer Center, led by Drs. Clapper, Treat and Bodor, is investigating the cause of lung cancer among never-smokers, and developing new strategies to treat the EGFR-mutated tumors that develop in this population. Most exciting is the novel finding that normal lung cells take on the features of tumors when exposed chronically to metabolites of the female hormone estrogen. Using a highly sensitive assay established by the group to measure metabolite levels, the team demonstrated that patients with EGFR-mutated lung cancer produce more of the putative cancer-causing estrogen metabolite than healthy people. Results from associated experimentation in the lab indicate that blocking the production of these “bad” estrogens in mice leads to a dramatic reduction in lung tumors, and awakens the immune system to attack these tumors.
Fox Chase Cancer Center’s unique environment supports the rapid movement of discoveries from the research labs to the patients who will benefit most. Current efforts are focused on using novel research findings to improve the treatment of lung cancer patients cared for in the Lung Cancer Clinic for Never Smokers at Fox Chase Cancer Center, the only clinic of its kind on the East Coast. Drug therapies are being developed that, when used in combination, are expected to both block the metabolism of estrogen and enhance the effectiveness of standard immunotherapy, which otherwise rarely works in never-smokers with lung cancer. To evaluate the risk of lung cancer conferred by specific metabolites of estrogen, their level is being measured in biofluids from never-smokers enrolled in clinical trials at Fox Chase Cancer Center and compared to that of healthy individuals.
Many questions remain unanswered and need to be addressed, including exactly how metabolites of estrogen cause never-smoking lung cancer, and why certain women face a higher risk of developing the disease. The team is planning to start a novel clinical trial soon to investigate if blocking the production of estrogen metabolites enhances the ability of standard immunotherapy drugs to attack lung tumors and inhibit their growth in never-smokers.
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