Adenosine Pathway in Genitourinary Malignancies: A Promising Immunotherapeutic Target

Abstract

AbstractPathways involved in adenosine metabolism have emerged as an exciting drug target in different types of cancers. Mechanistically it is proposed that there is a rapid increase in adenosine metabolism within the tumour microenvironment, which in turn suppress the immune-mediated tumour cell killing. Adenosine converting enzymes CD39 and CD73 and extracellular adenosine receptors A1, A2, A3 and A4 are regarded as the important regulators involved. Their expression in cancer cells are seen to be related to the tumour growth. Genitourinary cancer comprises of heterogenous group of tumours with different physiological function and nature of the organ system. During the last 5 years, new age immunotherapeutic drugs have revolutionized the treatment of different types of genitourinary cancers. Signalling components of adenosine pathway are thus promising since they, too, essentially modulate the immunotherapeutic targets. This review summarizes the literature on anticancer immunotherapeutic effect of adenosine pathway in genitourinary cancer. At first the mechanisms through which adenosine pathway exerts its immunosuppressive effect in different cancers are discussed. Thereafter, the preclinical and clinical validation of adenosine therapy in different types of genitourinary cancer are discussed. Subsequent to this, various ongoing multicancer clinical trials on the experimental drugs, targeting adenosine metabolism in genitourinary cancers, are tabulated with some perspective on the future research.KeywordsAdenosineTumour microenvironmentT cellMacrophageNatural killer cellsGenitourinary cancerImmunotherapyClinical trial