Microtubule-targeted agents: When mitochondria become essential to chemotherapy

Microtubule-Targeting Agents (MTAs) constitute a class of drugs largely used for cancer treatment in adults and children. In cancer cells, they suppress microtubule dynamics, and induce cell death via the mitochondrial intrinsic pathway. To date, links between mitochondria and microtubule network disturbance in MTAs mechanism of action are not obvious. The aim of the present contribution is to provide elements that could answer to the question: how far are mitochondria essential to anticancer chemotherapy that targets the microtubule cytoskeleton? We review the main molecular candidates to link microtubule alteration with the apoptotic mitochondrial pathway control. Involvement of direct targeting of mitochondria in MTA efficacy is also discussed. Furthermore, we line up current evidence and emerging concepts on the participation of both mitochondria and microtubule in MTA neurotoxic side effects. To decipher the interconnections between the mitochondrial and the microtubule networks may help to improve cancer cell response to chemotherapy. This article is part of a Special Issue entitled: Bioenergetics of Cancer.

Research highlights►Microtubule-Targeting Agents (MTAs) are largely used for cancer treatment. ►They suppress microtubule dynamics and initiate the apoptotic mitochondrial pathway. ►Here we review how far mitochondria are essential to anticancer chemotherapy. ►We also discussed links between mitochondria and microtubule network disturbances. ►Deciphering these two network interconnections may favor response to chemotherapy.