The interplay between cell signalling and the mevalonate pathway in cancer

The mevalonate (MVA) pathway is an essential metabolic pathway that uses acetyl-CoA to produce sterols and isoprenoids that are integral to tumour growth and progression. In recent years, many oncogenic signalling pathways have been shown to increase the activity and/or the expression of MVA pathway enzymes. This Review summarizes recent advances and discusses unique opportunities for immediately targeting this metabolic vulnerability in cancer with agents that have been approved for other therapeutic uses, such as the statin family of drugs, to improve outcomes for cancer patients.The authors thank J. van Leeuwen and W. B. Tu for helping to prepare this Review. The authors also thank other current and former members of the Penn laboratory for their helpful comments, including A. Pandyra, E. Chamberlain, J. De Melo, D. Dingar, A. Hickman, M. Kalkat, C. Lourenco, D. Resetca and A. Tamachi. The authors also acknowledge the many important contributions by their colleagues that could not be cited here owing to space and reference constraints. The funding agencies that enable the authors' research include the Ontario Institute for Cancer Research through funding provided by the Province of Ontario, the Canadian Institute for Health Research, Prostate Cancer Canada, the Department of Defense Breast Cancer Research Program, the Princess Margaret Cancer Foundation Hold'em for Life Prostate Cancer Research Fund, and the Terry Fox Foundation Canada. L.Z.P. holds the Canada Research Chair in Molecular Oncology