OXPHOS-targeting drugs in oncology: new perspectives. Expert Opin Ther Targets 2023;27(10):939-952
Date
09/22/2023Pubmed ID
37736880Pubmed Central ID
PMC11034819DOI
10.1080/14728222.2023.2261631Scopus ID
2-s2.0-85173986031 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
INTRODUCTION: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria-targeted modified natural compounds and US FDA-approved drugs with increased therapeutic index in cancer is discussed as an alternative strategy.
AREAS COVERED: Triphenylphosphonium cation (TPP+)-based drugs selectively accumulate in the mitochondria of cancer cells due to their increased negative membrane potential, target the oxidative phosphorylation proteins, inhibit mitochondrial respiration, and inhibit tumor proliferation. TPP+-based drugs exert minimal toxic side effects in rodents and humans. These drugs can sensitize radiation and immunotherapies.
EXPERT OPINION: TPP+-based drugs targeting the tumor mitochondrial electron transport chain are a new class of oxidative phosphorylation inhibitors with varying antiproliferative and antimetastatic potencies. Some of these TPP+-based agents, which are synthesized from naturally occurring molecules and FDA-approved drugs, have been tested in mice and did not show notable toxicity, including neurotoxicity, when used at doses under the maximally tolerated dose. Thus, more effort should be directed toward the clinical translation of TPP+-based OXPHOS-inhibiting drugs in cancer prevention and treatment.
Author List
Kalyanaraman B, Cheng G, Hardy M, You MAuthors
Gang Cheng PhD Assistant Professor in the Biophysics department at Medical College of WisconsinMicael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Drug Delivery Systems
Humans
Mice
Mitochondria
Neoplasms
Oxidative Phosphorylation
