{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:17:51Z","timestamp":1792603071232,"version":"4.5.0"},"reference-count":175,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB\/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K\/AKT\/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.<\/jats:p>","DOI":"10.3390\/cancers15030703","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T01:59:03Z","timestamp":1674525543000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Marianna","family":"Sirico","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8417-9172","authenticated-orcid":false,"given":"Alberto","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Bath, Bath BA2 7AY, UK"},{"name":"Department of Oncology, Royal United Hospital, Bath BA1 3NG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-6719","authenticated-orcid":false,"given":"Caterina","family":"Gianni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2467-749X","authenticated-orcid":false,"given":"Chiara","family":"Casadei","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Merloni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-2908","authenticated-orcid":false,"given":"Ugo","family":"De Giorgi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature12912","article-title":"Discovery and Saturation Analysis of Cancer Genes across 21 Tumour Types","volume":"505","author":"Lawrence","year":"2014","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/nrd1902","article-title":"Exploiting the PI3K\/AKT Pathway for Cancer Drug Discovery","volume":"4","author":"Hennessy","year":"2005","journal-title":"Nat. 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