Research ArticleCancer

A combination therapy for KRAS-driven lung adenocarcinomas using lipophilic bisphosphonates and rapamycin

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Science Translational Medicine  19 Nov 2014:
Vol. 6, Issue 263, pp. 263ra161
DOI: 10.1126/scitranslmed.3010382

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Bone Drugs’ Cousins Treating Cancer

Bisphosphonates are a class of drugs that are commonly used to treat osteoporosis and other disorders associated with bone resorption. A new group of related compounds called lipophilic bisphosphonates does not bind to bone, but has activity against some of the enzymes involved in the metabolism and activation of KRAS, a well-known oncogene. Here, Xia et al. show that lipophilic bisphosphonates are toxic to KRAS-mutant lung cancer cells in vitro. The lipophilic bisphosphonates alone were less effective in vivo, but rapamycin boosted their effectiveness in mouse models by facilitating autophagy and inhibiting a pathway that promotes tumor cell survival.

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