Inhibiting RRM2 to enhance the anticancer activity of chemotherapy

Biomed Pharmacother. 2021 Jan:133:110996. doi: 10.1016/j.biopha.2020.110996. Epub 2020 Nov 20.

Abstract

RRM2, the small subunit of ribonucleotide reductase, is identified as a tumor promotor and therapeutic target. It is common to see the overexpression of RRM2 in chemo-resistant cancer cells and patients. RRM2 mediates the resistance of many chemotherapeutic drugs and could become the predictor for chemosensitivity and prognosis. Therefore, inhibition of RRM2 may be an effective means to enhance the anticancer activity of chemotherapy. This review tries to discuss the mechanisms of RRM2 overexpression and the role of RRM2 in resistance to chemotherapy. Additionally, we compile the studies on small interfering RNA targets RRM2, RRM2 inhibitors, kinase inhibitors, and other ways that could overcome the resistance of chemotherapy or exert synergistic anticancer activity with chemotherapy through the expression inhibition or the enzyme inactivation of RRM2.

Keywords: Chemoresistance; Chemotherapy; Kinase inhibitors; RRM2 inhibitors; Ribonucleotide reductase subunit M2; Small interfering RNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • DNA Damage
  • DNA Repair
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / therapeutic use*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Ribonucleoside Diphosphate Reductase / antagonists & inhibitors*
  • Ribonucleoside Diphosphate Reductase / genetics
  • Ribonucleoside Diphosphate Reductase / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase