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Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents

Robert H Whitaker1, William J Placzek2

  • 1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA. rhwhitaker@uab.edu.

Cells
|April 25, 2019
PubMed

Insights

Microtubule targeting agents (MTAs) are standard cancer treatments that disrupt cell division. Emerging BCL2 inhibitors may overcome resistance to MTAs by targeting apoptosis regulators.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Microtubule targeting agents (MTAs) are a cornerstone of cancer chemotherapy.
  • Successful mitosis relies on precise microtubule dynamics for spindle formation and chromosome segregation.
  • Resistance to MTAs can arise from the amplification of anti-apoptotic BCL2 family proteins during cancer development.

Purpose of the Study:

  • To review the role of BCL2 family proteins in mediating resistance to microtubule targeting agents (MTAs).
  • To explore the therapeutic potential of combining MTAs with novel BCL2 family inhibitors.

Main Methods:

  • Literature review focusing on microtubule dynamics, apoptosis regulation, and cancer resistance mechanisms.
  • Analysis of the interplay between BCL2 family proteins and MTA efficacy.
  • Exploration of preclinical and clinical data on combination therapies.

Main Results:

  • BCL2 family proteins are key regulators of apoptosis and frequently dysregulated in cancer, contributing to MTA resistance.
  • Inhibiting BCL2 family proteins shows promise in restoring sensitivity to MTAs in preclinical models.
  • Combination strategies targeting both microtubules and BCL2 pathways may offer enhanced anti-cancer effects.

Conclusions:

  • Understanding BCL2 family regulation is crucial for overcoming MTA resistance in cancer treatment.
  • Combination therapy with MTAs and BCL2 inhibitors represents a promising strategy for improving patient outcomes in various malignancies.
Keywords:
apoptosisbcl2 familycell cyclecellular stresschemotherapymicrotubulemicrotubule targeting agentsmitosistubulin

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