The Role and Therapeutic Targeting of CCR5 in Breast Cancer
Abstract
The G-protein-coupled receptor C-C chemokine receptor 5 (CCR5) functions as a co-receptor for the entry of HIV into immune cells. CCR5 binds promiscuously to a diverse array of ligands initiating cell signaling that includes guided migration. Although well known to be expressed on immune cells, recent studies have shown the induction of CCR5 on the surface of breast cancer epithelial cells. The function of CCR5 on breast cancer epithelial cells includes the induction of aberrant cell survival signaling and tropism towards chemo attractants. As CCR5 is not expressed on normal epithelium, the receptor provides a potential useful target for therapy. Inhibitors of CCR5 (CCR5i), either small molecules (maraviroc, vicriviroc) or humanized monoclonal antibodies (leronlimab) have shown anti-tumor and anti-metastatic properties in preclinical studies. In early clinical studies, reviewed herein, CCR5i have shown promising results and evidence for effects on both the tumor and the anti-tumor immune response. Current clinical studies have therefore included combination therapy approaches with checkpoint inhibitors.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 08, 2023
- Source ID
- 10.3390/cells12182237
Entities
People
- Amanpreet S. Mahal
- Anthony W Ashton
- Dirk Jaeger
- Mustafa Alaziz
- Niels Halama
- Rasha Hamid
- Richard G Pestell
- Xuanmao Jiao
Organizations
- Baruch S. Blumberg Institute
- German Cancer Research Center
- Lankenau Institute for Medical Research
- National Institutes of Health
- United States Department of Defense
- University Hospital Heidelberg
- Xavier University