Abstract
Mitochondrial metabolism greatly influences cancer cell survival, invasion, metastasis, and resistance to many anticancer drugs. Furthermore, molecular-targeted therapies (e.g., oncogenic kinase inhibitors) create a dependence of surviving cells on mitochondrial metabolism. For these reasons, inhibition of mitochondrial metabolism represents promising therapeutic pathways in cancer. This review provides an overview of mitochondrial metabolism in cancer and discusses the limitations of mitochondrial inhibition for cancer treatment. Finally, we present preclinical evidence that mitochondrial inhibition could be associated with oncogenic “drivers” inhibitors, which may lead to innovative drug combinations for improving the efficacy of molecular-targeted therapy.
Highlights
IntroductionIntensive research has emerged to complete and further understand the initial observations of Warburg on cancer cell metabolism (for review [1])
Over the past decades, intensive research has emerged to complete and further understand the initial observations of Warburg on cancer cell metabolism
As a matter of fact, a recent analysis of tumor metabolomics indicates that cancer cells can oxidize glucose-derived pyruvate in mitochondria via the pyruvate dehydrogenase (PDH)-dependent pathway supporting the production of glutamine, which is mandatory for tumor growth [54]
Summary
Intensive research has emerged to complete and further understand the initial observations of Warburg on cancer cell metabolism (for review [1]). As recently reviewed [1], aberrant stimulation of prominent oncogenic signaling pathways such as the MAPK pathway increases glucose uptake and actively reroutes metabolism into glycolysis, providing the needed fuel and building blocks for cell survival and proliferation. These observations indicate that cancer cell metabolism constitutes one part of the aberrant oncogenedriven signaling resulting in the anarchic proliferation of cancer cells. Rather more than initially expected, mitochondrial metabolism plays a key role in cancer cell survival and development Given this crucial role of mitochondria at the core of cancer cell fate, the potential to interfere with mitochondrial functions has become a promising source of new targets for anticancer treatment. This review describes the promises and hurdles of targeting mitochondrial metabolism in cancer and discusses the advantages of integrating this innovative approach to current treatments such as molecular-targeted therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
