Recent Advances targeting CCR5 for Cancer and its Role in Immuno-Oncology
Abstract
Experiments of nature have revealed the peculiar importance of the G protein coupled receptor CCR5 in human disease since ancient times. The resurgence of interest in heterotypic signals in the onset and progression of tumorigenesis has led to the current focus of CCR5 as an exciting new therapeutic target for metastatic cancer with clinical trials now targeting breast and colon cancer. The eutopic expression of CCR5 activates calcium signaling and thereby augments Treg differentiation and migration to sites of inflammation. The misexpression of CCR5 in epithelial cells, induced upon oncogenic transformation, hijacks this migratory phenotype. CCR5 re-expression augments resistance to DNA damaging agents and is sufficient to induce cancer metastasis and “stemness”. Recent studies suggest important cross-talk between CCR5 signaling and immune checkpoint function. Because CCR5 on Tregs serves as the co-receptor for HIV virus entry, CCR5 targeted therapeutics used in HIV, (small molecules (maraviroc, vicroviroc) and a humanized monoclonal antibody (leronlimab)), are now being repositioned in clinical trials as cancer therapeutics. As CCR5 is expressed on a broad array of tumors, the opportunity for therapeutic repositioning and the rationale for combination therapy approaches are reviewed herein
Source and read in full
https://pmc.ncbi.nlm.nih.gov/articles/PMC6810651/
Abstract
Experiments of nature have revealed the peculiar importance of the G protein coupled receptor CCR5 in human disease since ancient times. The resurgence of interest in heterotypic signals in the onset and progression of tumorigenesis has led to the current focus of CCR5 as an exciting new therapeutic target for metastatic cancer with clinical trials now targeting breast and colon cancer. The eutopic expression of CCR5 activates calcium signaling and thereby augments Treg differentiation and migration to sites of inflammation. The misexpression of CCR5 in epithelial cells, induced upon oncogenic transformation, hijacks this migratory phenotype. CCR5 re-expression augments resistance to DNA damaging agents and is sufficient to induce cancer metastasis and “stemness”. Recent studies suggest important cross-talk between CCR5 signaling and immune checkpoint function. Because CCR5 on Tregs serves as the co-receptor for HIV virus entry, CCR5 targeted therapeutics used in HIV, (small molecules (maraviroc, vicroviroc) and a humanized monoclonal antibody (leronlimab)), are now being repositioned in clinical trials as cancer therapeutics. As CCR5 is expressed on a broad array of tumors, the opportunity for therapeutic repositioning and the rationale for combination therapy approaches are reviewed herein
Source and read in full
https://pmc.ncbi.nlm.nih.gov/articles/PMC6810651/
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