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.

Keywords:

• cancer
• cell metabolism
• drugs
• metabolism modulating agents
• Phase I and II

Acknowledgements

Timothy Schulz, PhD, Technical Resources International, Rockville, MD consulted on this project as a medical writer. DW Sborov and BM Haverkos contributed equally to this work.

Declaration of interest

DW Sborov and BM Haverkos are supported by the National Cancer Institute of the National Institutes of Health under Award Number T32CA165998 (PI Miguel Villalona and Steven Devine). Both are Hematology and Oncology fellows at Ohio State University. PJ Harris is an employee of the National Cancer Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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