Clusterin as modulator of carcinogenesis: A potential avenue for targeted cancer therapy

Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188500. doi: 10.1016/j.bbcan.2020.188500. Epub 2020 Dec 29.

Abstract

Clusterin (CLU) is an evolutionary conserved molecular chaperone present in different human tissues and fluids and established to be a significant cancer regulator. It controls several cancer-associated cellular events, including cancer cell proliferation, stemness, survival, metastasis, epithelial-mesenchymal transition, therapy resistance, and inhibition of programmed cell death to support cancer growth and recurrence. This multifunctional role of CLU makes it an ideal target for cancer control. More importantly, genetic and antisense-mediated (OGX-011) inhibition of CLU enhances the anticancer potential of different FDA-approved chemotherapeutic drugs at the clinical level, improving patient's survival. In this review, we have discussed the detailed mechanism of CLU-mediated modulation of different cancer-associated signaling pathways. We have also provided updated information on the current preclinical and clinical findings that drive trials in various cancer types for potential targeted cancer therapy.

Keywords: Cancer; Chemoresistance; Clusterin; EMT; Metastasis; Targeted cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clusterin / antagonists & inhibitors
  • Clusterin / genetics*
  • Clusterin / metabolism*
  • Drug Synergism
  • Drug Therapy
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Thionucleotides / pharmacology
  • Thionucleotides / therapeutic use

Substances

  • CLU protein, human
  • Clusterin
  • OGX-011
  • Thionucleotides