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The inhibitor of CCR5 block metastasis of v-Src oncogene-transformed prostate cancer

 

Prostate cancer is one of the most common cancer among men, but the molecular mechanism that leads to the disease relapse is not fully understood. Src family kinase (SFK) member Src kinase is involved in regulation of cancer cell proliferation, invasion, and metastasis, primarily to bone and brain. Sicoli et al. identified C-C chemokine receptor type 5 (CCR5) signaling activation is important for v-Src oncogene-transformed prostate cancer metastasis, and it antagonist can attenuate the burden. The article was published on Cancer Research.

 

Androgen ablation is the most common therapy for prostate cancer patients, but it cannot prevent subsequent relapse and metastasis, which are highly correlated with activities of Src signaling. Researchers found that Src oncogene transformation induced CCR5 signaling activity, via increasing expression levels of receptor and ligands associated with CCR5 signaling, in metastatic prostate cancer cells. The inhibition of the CCR5 signaling by its antagonist can reduce both bone and brain metastasis in vivo. The treatment of CCR5 inhibitor may be a promising therapeutic strategy for prostate cancer patients with activation of CCR5 signaling.

 

Reference:
Cancer Res. 2014 Dec 1;74(23):7103-14.

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S2003 Maraviroc Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM in cell-free assays, respectively. Maraviroc is used in the treatment of HIV infection.

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CCR