Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents

Cells. 2019 Apr 12;8(4):346. doi: 10.3390/cells8040346.

Abstract

Chemotherapeutic targeting of microtubules has been the standard of care in treating a variety of malignancies for decades. During mitosis, increased microtubule dynamics are necessary for mitotic spindle formation and successful chromosomal segregation. Microtubule targeting agents (MTAs) disrupt the dynamics necessary for successful spindle assembly and trigger programmed cell death (apoptosis). As the critical regulators of apoptosis, anti-apoptotic BCL2 family members are often amplified during carcinogenesis that can result in MTA resistance. This review outlines how BCL2 family regulation is positioned within the context of MTA treatment and explores the potential of combination therapy of MTAs with emerging BCL2 family inhibitors.

Keywords: apoptosis; bcl2 family; cell cycle; cellular stress; chemotherapy; microtubule; microtubule targeting agents; mitosis; tubulin.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Humans
  • Microtubules* / drug effects
  • Microtubules* / pathology
  • Mitosis / drug effects*
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2