August 16, 2018

A new target for lung cancer

Vanderbilt researchers have identified a new vulnerability in lung cancer — the transporter protein xCT — that may a therapeutic target for the disease.

Recent studies have discovered a role for the transporter protein xCT in the survival of different cancer cell types including breast, glioma and lymphoma. Smoking induces xCT expression in oral cancer cells, suggesting that this protein may also support lung tumor survival and progression.

Xiangming Ji, PhD, Pierre Massion, MD, and colleagues have now studied the role of xCT in non-small cell lung cancer (NSCLC). They demonstrated that xCT was highly expressed at the cell surface in NSCLC tumors and that elevated xCT correlated with advanced stage cancer and worse five-year survival in patients.

They found that blocking xCT transport activity with the drug sulfasalazine decreased cell proliferation and invasion in cell and animal models. They also showed that overexpression of xCT in normal airway epithelial cells increased cell dependence on the nutrient glutamine.

The findings, reported in the journal Oncogene, suggest that xCT regulates metabolic requirements during lung cancer progression and is a new vulnerability and potential therapeutic target in lung cancer. The study supports the need to develop small molecule inhibitors of xCT.

This research was supported by the National Institutes of Health (grant CA102353), the Department of Defense, and the FAMRI foundation.