Mitochondrial dynamics: biology and therapy in lung cancer

Expert Opin Investig Drugs. 2014 May;23(5):675-92. doi: 10.1517/13543784.2014.899350. Epub 2014 Mar 22.

Abstract

Introduction: Lung cancer mortality rates remain at unacceptably high levels. Although mitochondrial dysfunction is a characteristic of most tumor types, mitochondrial dynamics are often overlooked. Altered rates of mitochondrial fission and fusion are observed in lung cancer and can influence metabolic function, proliferation and cell survival.

Areas covered: In this review, the authors outline the mechanisms of mitochondrial fission and fusion. They also identify key regulatory proteins and highlight the roles of fission and fusion in metabolism and other cellular functions (e.g., proliferation, apoptosis) with an emphasis on lung cancer and the interaction with known cancer biomarkers. They also examine the current therapeutic strategies reported as altering mitochondrial dynamics and review emerging mitochondria-targeted therapies.

Expert opinion: Mitochondrial dynamics are an attractive target for therapeutic intervention in lung cancer. Mitochondrial dysfunction, despite its molecular heterogeneity, is a common abnormality of lung cancer. Targeting mitochondrial dynamics can alter mitochondrial metabolism, and many current therapies already non-specifically affect mitochondrial dynamics. A better understanding of mitochondrial dynamics and their interaction with currently identified cancer 'drivers' such as Kirsten-Rat Sarcoma Viral Oncogene homolog will lead to the development of novel therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Mitochondria / drug effects
  • Mitochondria / physiology*
  • Mitochondrial Dynamics / drug effects
  • Mitochondrial Dynamics / physiology*

Substances

  • Antineoplastic Agents