‘Unexpected’ Vulnerability Creates Treatment Opportunity in Aggressive Type of Lung Cancer

Researchers have identified a potentially critical weakness in lung cancers that have mutations in the KRAS gene, a cancer-promoting genetic alteration that has proven nearly impossible to target therapeutically. Moreover, the research team showed that a drug already being tested against other types of cancer could successfully exploit this vulnerability in KRAS mutant lung cancer cell lines and mouse models of lung cancer.

The weakness lies in the dependency of KRAS mutant lung cancer cells on a protein, called XPO1, that helps to shuttle molecules involved in important cellular functions from the cell nucleus into the surrounding cytoplasm. The XPO1 inhibitor shrank tumors in several different mouse models of non-small cell lung cancer (NSCLC)—the most common form of lung cancer—with KRAS mutations.

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