{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:24:36Z","timestamp":1776097476393,"version":"3.50.1"},"reference-count":92,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER)","award":["2021.07450.BD"],"award-info":[{"award-number":["2021.07450.BD"]}]},{"name":"Portuguese funds through Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Portuguese funds through Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["2021.07450.BD"],"award-info":[{"award-number":["2021.07450.BD"]}]},{"name":"CHAIR in Onco-Innovation","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"CHAIR in Onco-Innovation","award":["2021.07450.BD"],"award-info":[{"award-number":["2021.07450.BD"]}]},{"name":"FCT","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"FCT","award":["2021.07450.BD"],"award-info":[{"award-number":["2021.07450.BD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Ritonavir is a protease inhibitor initially developed for HIV treatment that is now used as a pharmacokinetic booster for other antiretrovirals due to it being a cytochrome P450 3A4 enzyme and P-glycoprotein inhibitor. Consequently, ritonavir is of special interest for repurposing in other diseases. It had an important role in battling the COVID-19 pandemic as a part of the developed drug Paxlovid\u00ae in association with nirmatrelvir and has shown effects in hepatitis and other pathogenic diseases. Ritonavir has also shown promising results in overcoming drug resistance and enhancing the efficacy of existing chemotherapeutic agents in oncology. Evidence of cancer repurposing potential was demonstrated in cancers such as ovarian, prostate, lung, myeloma, breast, and bladder cancer, with several mechanisms of action presented. In vitro studies indicate that ritonavir alone can inhibit key pathways involved in cancer cell survival and proliferation, causing apoptosis, cell cycle arrest, endoplasmic reticulum stress, and metabolic stress due to the inhibition of molecules like heat shock protein 90 and cyclin-dependent kinases. Ritonavir also causes resistant cells to become sensitized to anticancer drugs like gemcitabine or docetaxel. These findings indicate that repurposing ritonavir, either on its own or in combination with other medications, could be a promising approach for treating various diseases. This is particularly relevant in cancer therapy, where ritonavir repurposing is the central focus of this review.<\/jats:p>","DOI":"10.3390\/curroncol31100450","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T12:03:49Z","timestamp":1728389029000},"page":"6032-6049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Ritonavir\u2019s Evolving Role: A Journey from Antiretroviral Therapy to Broader Medical Applications"],"prefix":"10.3390","volume":"31","author":[{"given":"Mariana","family":"Pereira","sequence":"first","affiliation":[{"name":"PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"ref_1","unstructured":"DrugBank (2024, July 09). 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