Editors' ChoicePharmacology

Bone Drugs’ Cousins Treating Cancer

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Science Signaling  25 Nov 2014:
Vol. 7, Issue 353, pp. ec332
DOI: 10.1126/scisignal.aaa3449

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 inhibits enzymes involved in lipid modification (prenylation) of KRAS, which is encoded by a well-known oncogene. Xia et al. showed that lipophilic bisphosphonates were toxic to KRAS-mutant lung cancer cells in vitro. In vivo, combining the lipophilic bisphosphonates with rapamycin was more effective in reducing tumor growth in mice than treatment with the lipophilic bisphosphonates alone. Rapamycin facilitated autophagy, which prevented the activation of survival pathway in tumor cells exposed to lipophilic bisphosphonates, thereby resulting in a combination therapy with increased cytotoxicity.

Y. Xia, Y.-L. Liu, Y. Xie, W. Zhu, F. Guerra, S. Shen, N. Yeddula, W. Fischer, W. Low, X. Zhou, Y. Zhang, E. Oldfield, I. M. Verma, A combination therapy for KRAS-driven lung adenocarcinomas using lipophilic bisphosphonates and rapamycin. Sci. Transl. Med. 6, 263ra161 (2014). [Abstract]

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