Tubulin Proteins in Cancer Resistance: A Review

Curr Drug Metab. 2020;21(3):178-185. doi: 10.2174/1389200221666200226123638.

Abstract

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.

Keywords: Cancer; chemotherapy; resistance; tubulin; vinca; α-β-tubulin heterodimers..

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Microtubules / drug effects*
  • Microtubules / metabolism
  • Neoplasms
  • Taxoids / pharmacology
  • Tubulin / metabolism
  • Vinca Alkaloids / pharmacology

Substances

  • Antineoplastic Agents
  • Taxoids
  • Tubulin
  • Vinca Alkaloids