The G protein coupled receptor CCR5 in cancer.

The G coupled protein receptor CC chemokine receptor type 5 (CCR5) has the unusual characteristic in humans of being a developmentally non-essential gene that participates in several pathological processes including infection with HIV (Dean et al., 1996; Gupta et al., 2019; Samson et al., 1996), progression of stroke (Joy et al., 2019), osteoporosis (Xie et al., 2019) and the metastasis of cancer (Jiao et al., 2018; Velasco-Velazquez et al., 2012, 2014) (Reviewed in: Jiao, Nawab, et al., 2019; Jiao, Wang, & Pestell, 2019). The importance of CCR5 in HIV led to recent genetic engineering of humans to recreate a non-functional CCR5 gene. Thus, although the application of gene-editing tools, to manipulate human embryos is prohibited in the United States, and China. at the Second International Summit on Human Genome Editing in Hong Kong (http://www.nationalacademies.org/), it was claimed that CRISPR-Cas9 systems had been used to edit the CCR5 gene in twin baby girls. The importance of CCR5 in stroke has led to clinical trials using maraviroc (NCT03172026). The key function of CCR5 in cancer metastasis and homing (Jiao et al., 2018; Jiao, Nawab, et al., 2019; Velasco-Velazquez et al., 2012, 2014) has led to three active clinical trials for metastatic cancer using CCR5 antagonists (Jiao, Nawab, et al., 2019; Jiao, Wang, & Pestell, 2019). Thus, it was surprising to find that the all-cause mortality rate in individuals who are homozygous for the CCR5△32 allele in the United Kingdom normal population was increased >20% increase, with an almost 2 year reduction overall lifespan (Wei & Nielsen, 2019). The current review herein discusses the distinct functions of CCR5 in human disease and potential avenues for further research.