The therapeutic potential of targeting CD73 and CD73-derived adenosine in melanoma.

The therapeutic potential of targeting CD73 and CD73-derived adenosine in melanoma. Biochimie. 2020 Jun 22;: Authors: Soleimani A, Farshchi HK, Mirzavi F, Zamani P, Ghaderi A, Amini Y, Khorrami S, Mashayekhi K, Jaafari MR Abstract The hypoxic environment of melanoma results in CD73 upregulation on the surface of various tumor microenvironment (TME) cells including tumor cells, stromal cells and infiltrated immune cells. Consequently, CD73 through both enzymatic and none enzymatic functions affect melanoma progression. Overaccumulation of CD73-derived adenosine through interaction with its four G coupled receptors (A1AR, A2AAR, A2BAR, and A3AR) mediate tumor growth, immune suppression, angiogenesis, and metastasis. This paper aims to comprehensively review the therapeutic potential of CD73 ectonucleotidase targeting in melanoma. To reach this goal, firstly, we summarize the structure, function, regulation, and clinical outcome of CD73 ectonucleotidase. Then, we depict the metabolism and signaling of CD73-derived adenosine along with its progressive role in development of melanoma. Furthermore, the therapeutic potentials of CD73 -adenosine axis targeting is assessed in both preclinical and clinical studies. Targeting CD73-derived adenosine via small molecule inhibitor or monoclonal antibodies studies especially in combination with immune checkpoint blockers including PD-1 and CTLA-4 have shown desirable results for management of melano...
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research