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Non-small cell lung cancer (NSCLC)

Serine/threonine kinase 11 (STK11; LKB1); K-Ras

Mouse and cell culture studies suggest the metformin analog phenformin could help treat K-Ras-driven NSCLCs with LKB1 mutations. In an LKB1-deficient human NSCLC cell line, phenformin induced apoptosis, whereas metformin did not. In mice bearing K-Ras-driven Lkb1-deficient NSCLC tumors, oral phenformin led to lower tumor burden and greater survival than vehicle. Next steps could include testing phenformin in additional models of LKB1-deficient cancers.
Metformin is a generic drug approved to treat diabetes and is in clinical testing to treat various cancers.
Phenformin was previously marketed to treat diabetes but was withdrawn by the FDA in 1978 due to toxicity.

SciBX 6(6); doi:10.1038/scibx.2013.138
Published online Feb. 14, 2013

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Shackelford, D.B. et al. Cancer Cell; published online Jan. 24, 2013;
Contact: Reuben J. Shaw, Salk Institute for Biological Studies, La Jolla, Calif.
Contact: David B. Shackelford, same affiliation as above