Therapeutic Perspectives of HIV-Associated Chemokine Receptor (CCR5 and CXCR4) Antagonists in Carcinomas

Int J Mol Sci. 2022 Dec 28;24(1):478. doi: 10.3390/ijms24010478.

Abstract

The interaction between malignant cells and the tumor microenvironment is critical for tumor progression, and the chemokine ligand/receptor axes play a crucial role in this process. The CXCR4/CXCL12 and CCR5/CCL5 axes, both related to HIV, have been associated with the early (epithelial-mesenchymal transition and invasion) and late events (migration and metastasis) of cancer progression. In addition, these axes can also modulate the immune response against tumors. Thus, antagonists against the receptors of these axes have been proposed in cancer therapy. Although preclinical studies have shown promising results, clinical trials are needed to include these drugs in the oncological treatment protocols. New alternatives for these antagonists, such as dual CXCR4/CCR5 antagonists or combined therapy in association with immunotherapy, need to be studied in cancer therapy.

Keywords: cancer therapy; chemokines; immunotherapy; oncology.

Publication types

  • Review

MeSH terms

  • CCR5 Receptor Antagonists* / therapeutic use
  • Carcinoma* / drug therapy
  • Chemokine CXCL12
  • Humans
  • Receptors, CCR5
  • Receptors, CXCR4* / antagonists & inhibitors
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • CCR5 protein, human
  • Chemokine CXCL12
  • CXCR4 protein, human
  • Receptors, CCR5
  • Receptors, CXCR4
  • CCR5 Receptor Antagonists