Background: Targeting cancer metabolism is a promising strategy in improving cancer treatment.
Objective: To introduce a targeted therapy with topical 3-bromopyruvate (3BP), aglycolytic inhibitor, into the clinic in the near future.
Method: We investigated the anti-tumor efficacy of 3BP on melanoma cells in vitro and in a preclinical model.
Results: Our cell-based study demonstrated that 3BP showed cytotoxicity for melanoma cells under anchorage-dependent or independent cell growth via a reactive oxygen species-mediated and caspase-independent cell death pathway. Moreover, 3BP inhibited both self-renewal potential and growth of slow-cycling phenotype in melanoma cells. Remarkably, the preclinical mouse xenograft model shed light on topical application of 3BP, showing significant anti-tumor effects with no apparent toxicity in surrounding normal tissues.
Conclusion: We have now proposed that a targeted therapy with topical 3BP is an innovative strategy for adjuvant chemotherapy of technically or medically unresectable melanoma and possibly other skin cancers.
Keywords: 3-bromopyruvateglycolytic inhibitormelanoma; Topical application.
Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.