The Role and Therapeutic Targeting of CCR5 in Breast Cancer.
Rasha HamidMustafa AlazizAmanpreet S MahalAnthony W AshtonNiels HalamaDirk JaegerXuanmao JiaoRichard G PestellPublished in: Cells (2023)
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.
Keyphrases
- dendritic cells
- regulatory t cells
- combination therapy
- immune response
- squamous cell carcinoma
- small cell lung cancer
- cell therapy
- dna damage
- cancer therapy
- hiv positive
- inflammatory response
- radiation therapy
- mesenchymal stem cells
- high resolution
- toll like receptor
- south africa
- hiv testing
- human immunodeficiency virus
- cell proliferation
- men who have sex with men
- locally advanced
- human health
- replacement therapy