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The David H. Koch Institute for Integrative Cancer Research at MITThe David H. Koch Institute for Integrative Cancer Research at MIT

Massachusetts Institute of Technology

National Cancer Institute Cancer Center

Science + Engineering... Conquering Cancer Together

Keap-ing Lung Cancer in Check

Lung cancer cells driven by KRAS oncogene

Lung cancer cells driven by KRAS oncogene. Credit: National Cancer Institute / Huntsman Cancer Institute at the Univ. of Utah

The Jacks Lab identified a new therapeutic target for an aggressive form of lung cancer. Lung adenocarcinoma accounts for about 40 percent of lung cancers in the U.S., with 20–30% of lung adenocarcinomas harboring mutations in the gene KEAP1. In previous work, the group showed that lung adenocarcinomas that are mutated for both KRAS and KEAP1 are highly aggressive and dependent on the breakdown of glutamine—paving the way for clinical trials of glutaminase inhibitors in combination with other therapies that target KEAP1-mutant non-small cell lung cancers.

In a new study, led by graduate student Rodrigo Romero and appearing in Nature Cancer, researchers screened of a library of genes that are known or predicted to be druggable in a comprehensive and systematic search for new therapeutic targets for KEAP1 mutant non-small cell lung cancers. The screens identified the gene Slc33a1, as well as several other genes that are associated with the unfolded protein response, a process key to cell viability. Tests in cell lines and in mouse models showed a strong dependency for Slc33a1 in non-small cell lung cancers, suggesting that patients with Keap1-mutant tumors may respond to SLC33A1 inhibition.