| First Author | Shackelford DB | Year | 2013 |
| Journal | Cancer Cell | Volume | 23 |
| Issue | 2 | Pages | 143-58 |
| PubMed ID | 23352126 | Mgi Jnum | J:194330 |
| Mgi Id | MGI:5473446 | Doi | 10.1016/j.ccr.2012.12.008 |
| Citation | Shackelford DB, et al. (2013) LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell 23(2):143-58 |
| abstractText | The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in approximately 20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, making LKB1-deficient cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified phenformin, a mitochondrial inhibitor and analog of the diabetes therapeutic metformin, as selectively inducing apoptosis in LKB1-deficient NSCLC cells. Therapeutic trials in Kras-dependent mouse models of NSCLC revealed that tumors with Kras and Lkb1 mutations, but not those with Kras and p53 mutations, showed selective response to phenformin as a single agent, resulting in prolonged survival. This study suggests phenformin as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors. |
