title: Investigational cancer drugs targeting cell metabolism in clinical development.
abstract: Introduction: Malignant cell transformation and tumor progression are associated with alterations in glycolysis, fatty acid synthesis, amino acid delivery and production of reactive oxygen species. With increased understanding of the role of metabolism in tumors, there has been interest in developing agents that target tumor specific metabolic pathways. Numerous promising agents targeting altered metabolic pathways are currently in Phase I - III clinical trials. Areas covered: This paper reviews the early phase clinical trial development of these agents and provides perspective on the future direction of this emerging field. Specifically, the authors describe novel and repurposed therapies, focusing on the effects of each agent on tumor metabolism and results from relevant Phase I and II clinical trials. Expert opinion: Metabolism modulating agents, alone and in combinations with other classes of agents, have shown efficacy in the treatment of neoplasm, which, the authors believe, will bear positive results in future studies. Because of the significant crosstalk between metabolic pathways and oncogenic signaling pathways, the authors also believe that combining metabolic modifiers with targeted agents will be an important strategy. An increased understanding of cancer metabolism, in addition to the continued study of metabolic modulators, should lead to further advances in this nascent therapeutic field in the future.
authors.affiliation: Ohio State University, Department of Internal Medicine , Columbus, OH , USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Sborov
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Haverkos
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Harris
keywords: Phase I and II; cancer; cell metabolism; drugs; metabolism modulating agents