Targeting the B-cell lymphoma 2 anti-apoptotic proteins for cervical cancer treatment

Future Oncol. 2020 Oct;16(28):2235-2249. doi: 10.2217/fon-2020-0389. Epub 2020 Jul 26.

Abstract

The B-cell lymphoma 2 (BCL-2) anti-apoptotic proteins have become attractive therapeutic targets especially with the development of BH3-mimetics which selectively target these proteins. However, it is important to note that expression levels of the anti-apoptotic proteins and their relevance in inhibiting apoptosis varies between different cell lineages. This addiction to certain anti-apoptotic proteins for survival, can be determined with various techniques and targeted effectively with selective BH3-mimetics. Studies have highlighted that anti-apoptotic proteins BCL-XL and MCL-1 are crucial for cervical cancer cell survival. Co-targeting BCL-XL and MCL-1 with selective BH3-mimetics yielded promising results in cervical cancer cell lines. In this review, we focus on the expression levels of the anti-apoptotic proteins in cervical cancer tissues and how to possibly target them with BH3-mimetics.

Keywords: BCL-2 selective inhibitors; BCL-XL selective inhibitors; BH3-mimetics; MCL-1 selective inhibitors; cervical cancer.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Disease Progression
  • Female
  • Humans
  • Molecular Structure
  • Molecular Targeted Therapy
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Uterine Cervical Neoplasms / etiology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BCL2 protein, human
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2