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Indeed, in addition to its initial clinical application as an anti-hypertensive drug in\nthe pulmonary system, Sildenafil is also known for its beneficial effects in erectile dysfunction.\nMoreover, evidence has been accumulated to support its value in anti-cancer therapy,\neither alone or in combination with other clinically efficient chemotherapy drugs. In this review,\nwe focused on the old and recent in vitro and in vivo studies demonstrating the cellular\nand molecular rationale for the application of Sildenafil in combination therapy in various\ntypes of cancer. We emphasized on the different molecular targets as well as the different signaling\npathways involved in cancer cells. The pro-apoptotic effect of Sildenafil through nitric\noxide (NO)\/ phosphodiesterase type 5 (PDE5)-dependent manner seems to be one of the most\ncommon mechanisms. However, the activation of autophagy, as well as the modulation of the\nanti-tumor immunity, constitutes the other pathways triggered by Sildenafil. Overall, the studies\nconverged to reveal the complexity of the anti-cancer potential of Sildenafil. Thus, through\nour review, we aimed to present an updated and simplified picture of such repurposing of\nSildenafil in the field of oncology.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867327666200730165338","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T17:31:53Z","timestamp":1596475913000},"page":"2248-2259","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sildenafil in Combination Therapy against Cancer: A Literature Review"],"prefix":"10.2174","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-0378","authenticated-orcid":true,"given":"Rabah","family":"Iratni","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, United Arab Emirates University, P.O. Box: 15551, Al Ain,United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0022-578X","authenticated-orcid":true,"given":"Mohammed Akli","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, United Arab Emirates University, P.O. Box: 15551, Al Ain,United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1468","volume":"3","author":"Ashburn T.T.","year":"2004","unstructured":"Ashburn T.T.; Thor K.B.; Drug repositioning: identifying and developing new uses for existing drugs. 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