{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:01:27Z","timestamp":1791860487597,"version":"4.3.4"},"reference-count":428,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Collaborative Advancement Grants Program-Strategic Teams Office of Research, University of Cincinnati","award":["R40309"],"award-info":[{"award-number":["R40309"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K\/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted.<\/jats:p>","DOI":"10.3390\/ijms22073464","type":"journal-article","created":{"date-parts":[[2021,3,28]],"date-time":"2021-03-28T22:09:01Z","timestamp":1616969341000},"page":"3464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":274,"title":["PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9808-8797","authenticated-orcid":false,"given":"Rosalin","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hima","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-7227","authenticated-orcid":false,"given":"Samar","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2922-4476","authenticated-orcid":false,"given":"Mary Kate","family":"Kilroy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan T.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K Pathway in Human Disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrclinonc.2018.28","article-title":"Targeting the PI3K pathway in cancer: Are we making headway?","volume":"15","author":"Janku","year":"2018","journal-title":"Nat. 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