{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:09:52Z","timestamp":1787987392755,"version":"build-2784847793"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Diagn Ther"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s40291-025-00815-4","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T10:26:48Z","timestamp":1758191208000},"page":"5-17","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-5951","authenticated-orcid":false,"given":"Ioannis A.","family":"Voutsadakis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"issue":"4","key":"815_CR1","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","volume":"170","author":"DA Fruman","year":"2017","unstructured":"Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605\u201335. https:\/\/doi.org\/10.1016\/j.cell.2017.07.029.","journal-title":"Cell"},{"issue":"7407","key":"815_CR2","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nature11252","volume":"487","author":"CGA Network","year":"2012","unstructured":"Network CGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330\u20137. https:\/\/doi.org\/10.1038\/nature11252.","journal-title":"Nature"},{"issue":"3","key":"815_CR3","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.clcc.2021.02.003","volume":"20","author":"IA Voutsadakis","year":"2021","unstructured":"Voutsadakis IA. The landscape of PIK3CA mutations in colorectal cancer. Clin Colorectal Cancer. 2021;20(3):201\u201315. https:\/\/doi.org\/10.1016\/j.clcc.2021.02.003.","journal-title":"Clin Colorectal Cancer"},{"key":"815_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2023.103987","volume":"186","author":"IA Voutsadakis","year":"2023","unstructured":"Voutsadakis IA. KRAS mutated colorectal cancers with or without PIK3CA mutations: clinical and molecular profiles inform current and future therapeutics. Crit Rev Oncol Hematol. 2023;186:103987. https:\/\/doi.org\/10.1016\/j.critrevonc.2023.103987.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"Pt 5","key":"815_CR5","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1242\/jcs.093773","volume":"127","author":"S Jean","year":"2014","unstructured":"Jean S, Kiger AA. Classes of phosphoinositide 3-kinases at a glance. J Cell Sci. 2014;127(Pt 5):923\u20138. https:\/\/doi.org\/10.1242\/jcs.093773.","journal-title":"J Cell Sci"},{"issue":"4","key":"815_CR6","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.celrep.2016.03.075","volume":"15","author":"M Giannakis","year":"2016","unstructured":"Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, Nishihara R, et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep. 2016;15(4):857\u201365. https:\/\/doi.org\/10.1016\/j.celrep.2016.03.075.","journal-title":"Cell Rep"},{"issue":"1","key":"815_CR7","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ccell.2017.12.004","volume":"33","author":"R Yaeger","year":"2018","unstructured":"Yaeger R, Chatila WK, Lipsyc MD, Hechtman JF, Cercek A, Sanchez-Vega F, et al. Clinical sequencing defines the genomic landscape of metastatic colorectal cancer. Cancer Cell. 2018;33(1):125-136.e3. https:\/\/doi.org\/10.1016\/j.ccell.2017.12.004.","journal-title":"Cancer Cell"},{"issue":"11","key":"815_CR8","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/nm.3967","volume":"21","author":"J Guinney","year":"2015","unstructured":"Guinney J, Dienstmann R, Wang X, de Reyni\u00e8s A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350\u20136. https:\/\/doi.org\/10.1038\/nm.3967.","journal-title":"Nat Med"},{"issue":"1","key":"815_CR9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.clcc.2020.09.003","volume":"20","author":"HJ Lenz","year":"2021","unstructured":"Lenz HJ, Argiles G, Yoshino T, Tejpar S, Ciardiello F, Braunger J, et al. Association of consensus molecular subtypes and molecular markers with clinical outcomes in patients with metastatic colorectal cancer: biomarker analyses from LUME-colon 1. Clin Colorectal Cancer. 2021;20(1):84-95.e8. https:\/\/doi.org\/10.1016\/j.clcc.2020.09.003.","journal-title":"Clin Colorectal Cancer"},{"issue":"7","key":"815_CR10","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1158\/1078-0432.CCR-20-3652","volume":"27","author":"P Narayan","year":"2021","unstructured":"Narayan P, Prowell TM, Gao JJ, Fernandes LL, Li E, Jiang X, et al. FDA approval summary: alpelisib plus fulvestrant for patients with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer. Clin Cancer Res. 2021;27(7):1842\u20139. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-3652.","journal-title":"Clin Cancer Res"},{"key":"815_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/BLCTT.S309171","volume":"13","author":"N Bou Zeid","year":"2023","unstructured":"Bou Zeid N, Yazbeck V. PI3k inhibitors in NHL and CLL: an unfulfilled promise. Blood Lymphat Cancer. 2023;13:1\u201312. https:\/\/doi.org\/10.2147\/BLCTT.S309171.","journal-title":"Blood Lymphat Cancer."},{"issue":"7418","key":"815_CR12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","volume":"490","author":"CGA Network","year":"2012","unstructured":"Network CGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61\u201370. https:\/\/doi.org\/10.1038\/nature11412.","journal-title":"Nature"},{"issue":"17","key":"815_CR13","doi-asserted-by":"publisher","first-page":"5132","DOI":"10.3390\/jcm11175132","volume":"11","author":"IA Voutsadakis","year":"2022","unstructured":"Voutsadakis IA. The genomic environment of BRAF mutated and BRAF\/PIK3CA double mutated colorectal cancers. J Clin Med. 2022;11(17):5132. https:\/\/doi.org\/10.3390\/jcm11175132.","journal-title":"J Clin Med"},{"issue":"10","key":"815_CR14","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.3390\/medicina58101498","volume":"58","author":"IA Voutsadakis","year":"2022","unstructured":"Voutsadakis IA. Sensitivities and dependencies of BRAF mutant colorectal cancer cell lines with or without PIK3CA mutations for discovery of vulnerabilities with therapeutic potential. Medicina (Kaunas). 2022;58(10):1498. https:\/\/doi.org\/10.3390\/medicina58101498.","journal-title":"Medicina (Kaunas)"},{"issue":"20","key":"815_CR15","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","volume":"380","author":"F Andr\u00e9","year":"2019","unstructured":"Andr\u00e9 F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929\u201340. https:\/\/doi.org\/10.1056\/NEJMoa1813904.","journal-title":"N Engl J Med"},{"issue":"2","key":"815_CR16","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s10549-018-4792-0","volume":"171","author":"S Jain","year":"2018","unstructured":"Jain S, Shah AN, Santa-Maria CA, Siziopikou K, Rademaker A, Helenowski I, et al. Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy. Breast Cancer Res Treat. 2018;171(2):371\u201381. https:\/\/doi.org\/10.1007\/s10549-018-4792-0.","journal-title":"Breast Cancer Res Treat"},{"issue":"14","key":"815_CR17","doi-asserted-by":"publisher","first-page":"3867","DOI":"10.1158\/1078-0432.CCR-21-0047","volume":"27","author":"K Jhaveri","year":"2021","unstructured":"Jhaveri K, Drago JZ, Shah PD, Wang R, Pareja F, Ratzon F, et al. A phase I study of alpelisib in combination with trastuzumab and LJM716 in patients with PIK3CA-mutated HER2-positive metastatic breast cancer. Clin Cancer Res. 2021;27(14):3867\u201375. https:\/\/doi.org\/10.1158\/1078-0432.CCR-21-0047.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"815_CR18","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1200\/JCO.20.02088","volume":"39","author":"J Tabernero","year":"2021","unstructured":"Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol. 2021;39(4):273\u201384. https:\/\/doi.org\/10.1200\/JCO.20.02088.","journal-title":"J Clin Oncol"},{"issue":"19","key":"815_CR19","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1200\/JCO-24-02026","volume":"43","author":"F Pietrantonio","year":"2025","unstructured":"Pietrantonio F, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, et al. Overall survival analysis of the phase III CodeBreaK 300 study of sotorasib plus panitumumab versus investigator\u2019s choice in chemorefractory KRAS G12C colorectal cancer. J Clin Oncol. 2025;43(19):2147\u201354. https:\/\/doi.org\/10.1200\/JCO-24-02026.","journal-title":"J Clin Oncol"},{"issue":"10","key":"815_CR20","doi-asserted-by":"publisher","first-page":"4341","DOI":"10.21873\/anticanres.16629","volume":"43","author":"M Kataoka","year":"2023","unstructured":"Kataoka M, Kitazawa M, Nakamura S, Koyama M, Yamamoto Y, Miyazaki S, et al. Cetuximab enhances the efficacy of MRTX1133, a novel KRASG12D inhibitor, in colorectal cancer treatment. Anticancer Res. 2023;43(10):4341\u20138. https:\/\/doi.org\/10.21873\/anticanres.16629.","journal-title":"Anticancer Res"},{"issue":"13","key":"815_CR21","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1200\/JCO.2017.72.7107","volume":"36","author":"D Juric","year":"2018","unstructured":"Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, et al. Phosphatidylinositol 3-kinase \u03b1-selective inhibition with alpelisib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study. J Clin Oncol. 2018;36(13):1291\u20139. https:\/\/doi.org\/10.1200\/JCO.2017.72.7107.","journal-title":"J Clin Oncol"},{"issue":"1","key":"815_CR22","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1158\/1078-0432.CCR-14-0947","volume":"21","author":"D Sarker","year":"2015","unstructured":"Sarker D, Ang JE, Baird R, Kristeleit R, Shah K, Moreno V, et al. First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2015;21(1):77\u201386. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-0947.","journal-title":"Clin Cancer Res"},{"key":"815_CR23","doi-asserted-by":"publisher","DOI":"10.1200\/PO.21.00424","volume":"6","author":"IE Krop","year":"2022","unstructured":"Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, et al. Phase II study of taselisib in PIK3CA-mutated solid tumors other than breast and squamous lung cancer: results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol I. JCO Precis Oncol. 2022;6:e2100424. https:\/\/doi.org\/10.1200\/PO.21.00424.","journal-title":"JCO Precis Oncol"},{"issue":"14","key":"815_CR24","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1200\/JCO.21.01648","volume":"40","author":"S Damodaran","year":"2022","unstructured":"Damodaran S, Zhao F, Deming DA, Mitchell EP, Wright JJ, Gray RJ, et al. Phase II study of copanlisib in patients with tumors with PIK3CA mutations: results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocol Z1F. J Clin Oncol. 2022;40(14):1552\u201361. https:\/\/doi.org\/10.1200\/JCO.21.01648.","journal-title":"J Clin Oncol"},{"key":"815_CR25","doi-asserted-by":"publisher","first-page":"1390452","DOI":"10.3389\/fonc.2024.1390452","volume":"14","author":"AR Lim","year":"2024","unstructured":"Lim AR, Kim B, Kim JH, Hyun MH, Park KH, Kim YH, et al. Phase Ib and pharmacokinetics study of alpelisib, a PIK3CA inhibitor, and capecitabine in patients with advanced solid tumors. Front Oncol. 2024;14:1390452. https:\/\/doi.org\/10.3389\/fonc.2024.1390452.","journal-title":"Front Oncol"},{"issue":"1","key":"815_CR26","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1158\/2159-8290.CD-23-0467","volume":"14","author":"SP Suehnholz","year":"2024","unstructured":"Suehnholz SP, Nissan MH, Zhang H, Kundra R, Nandakumar S, Lu C, et al. Quantifying the expanding landscape of clinical actionability for patients with cancer. Cancer Discov. 2024;14(1):49\u201365. https:\/\/doi.org\/10.1158\/2159-8290.CD-23-0467.","journal-title":"Cancer Discov"},{"key":"815_CR27","doi-asserted-by":"publisher","DOI":"10.1200\/PO.17.00011","author":"D Chakravarty","year":"2017","unstructured":"Chakravarty D, Gao J, Phillips SM, Kundra R, Zhang H, Wang J, et al. OncoKB: a precision oncology knowledge base. JCO Precis Oncol. 2017. https:\/\/doi.org\/10.1200\/PO.17.00011.","journal-title":"JCO Precis Oncol"},{"issue":"4","key":"815_CR28","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.clcc.2016.03.004","volume":"15","author":"DW Bowles","year":"2016","unstructured":"Bowles DW, Kochenderfer M, Cohn A, Sideris L, Nguyen N, Cline-Burkhardt V, et al. A randomized, phase II trial of cetuximab with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with metastatic colorectal carcinoma. Clin Colorectal Cancer. 2016;15(4):337-344.e2. https:\/\/doi.org\/10.1016\/j.clcc.2016.03.004.","journal-title":"Clin Colorectal Cancer"},{"issue":"4","key":"815_CR29","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1007\/s10637-019-00814-3","volume":"38","author":"R Goodwin","year":"2020","unstructured":"Goodwin R, Jonker D, Chen E, Kennecke H, Cabanero M, Tsao MS, et al. A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer. Invest New Drugs. 2020;38(4):1077\u201384. https:\/\/doi.org\/10.1007\/s10637-019-00814-3.","journal-title":"Invest New Drugs"},{"issue":"6","key":"815_CR30","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1158\/2159-8290.CD-16-0795","volume":"7","author":"RMJM van Geel","year":"2017","unstructured":"van Geel RMJM, Tabernero J, Elez E, Bendell JC, Spreafico A, Schuler M, et al. A phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. Cancer Discov. 2017;7(6):610\u20139. https:\/\/doi.org\/10.1158\/2159-8290.CD-16-0795.","journal-title":"Cancer Discov"},{"issue":"1","key":"815_CR31","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41416-020-01147-2","volume":"124","author":"SCFA Huijberts","year":"2021","unstructured":"Huijberts SCFA, Boelens MC, Bernards R, Opdam FL. Mutational profiles associated with resistance in patients with BRAFV600E mutant colorectal cancer treated with cetuximab and encorafenib +\/\u2212 binimetinib or alpelisib. Br J Cancer. 2021;124(1):176\u201382. https:\/\/doi.org\/10.1038\/s41416-020-01147-2.","journal-title":"Br J Cancer"},{"issue":"Suppl 5","key":"815_CR32","doi-asserted-by":"publisher","first-page":"S573","DOI":"10.1016\/j.annonc.2021.08.1008","volume":"32","author":"S Capano","year":"2021","unstructured":"Capano S, Merlino G, Bigioni M, Tunici P, Cottino F, Zanella E, et al. M EN1611 in combination with cetuximab: targeting PIK3CA mutations in RAS-wild-type patient-derived colorectal cancer xenografts. Ann Oncol. 2021;32(Suppl 5):S573.","journal-title":"Ann Oncol"},{"issue":"1","key":"815_CR33","doi-asserted-by":"publisher","first-page":"4332","DOI":"10.1038\/s41467-025-59588-3","volume":"16","author":"X Qu","year":"2025","unstructured":"Qu X, Hamidi H, Johnson RM, Sokol ES, Lin E, Eng C, et al. Ligand-activated EGFR\/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer. Nat Commun. 2025;16(1):4332. https:\/\/doi.org\/10.1038\/s41467-025-59588-3.","journal-title":"Nat Commun"},{"issue":"1","key":"815_CR34","doi-asserted-by":"publisher","first-page":"15365","DOI":"10.1038\/s41598-019-51981-5","volume":"9","author":"SM Bray","year":"2019","unstructured":"Bray SM, Lee J, Kim ST, Hur JY, Ebert PJ, Calley JN, et al. Genomic characterization of intrinsic and acquired resistance to cetuximab in colorectal cancer patients. Sci Rep. 2019;9(1):15365. https:\/\/doi.org\/10.1038\/s41598-019-51981-5.","journal-title":"Sci Rep"},{"issue":"3","key":"815_CR35","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/s41591-023-02791-w","volume":"30","author":"K Shitara","year":"2024","unstructured":"Shitara K, Muro K, Watanabe J, Yamazaki K, Ohori H, Shiozawa M, et al. Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. Nat Med. 2024;30(3):730\u20139. https:\/\/doi.org\/10.1038\/s41591-023-02791-w.","journal-title":"Nat Med"},{"issue":"6","key":"815_CR36","doi-asserted-by":"publisher","first-page":"859","DOI":"10.3390\/cancers11060859","volume":"11","author":"AM Rachiglio","year":"2019","unstructured":"Rachiglio AM, Lambiase M, Fenizia F, Roma C, Cardone C, Iannaccone A, et al. Genomic profiling of KRAS\/NRAS\/BRAF\/PIK3CA wild-type metastatic colorectal cancer patients reveals novel mutations in genes potentially associated with resistance to anti-EGFR agents. Cancers (Basel). 2019;11(6):859. https:\/\/doi.org\/10.3390\/cancers11060859.","journal-title":"Cancers (Basel)"},{"issue":"1\u20132","key":"815_CR37","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/14622416.2025.2479414","volume":"26","author":"IA Voutsadakis","year":"2025","unstructured":"Voutsadakis IA. Treatment of extended RAS\/BRAF wild-type metastatic colorectal cancer with anti-EGFR antibody combinations. Pharmacogenomics. 2025;26(1\u20132):39\u201352. https:\/\/doi.org\/10.1080\/14622416.2025.2479414.","journal-title":"Pharmacogenomics"},{"key":"815_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.19.00221","volume":"3","author":"DM Hyman","year":"2019","unstructured":"Hyman DM, Tran B, Paz-Ares L, Machiels JP, Schellens JH, Bedard PL, et al. Combined PIK3CA and FGFR inhibition with alpelisib and infigratinib in patients with PIK3CA-mutant solid tumors, with or without FGFR alterations. JCO Precis Oncol. 2019;3:1\u201313. https:\/\/doi.org\/10.1200\/PO.19.00221.","journal-title":"JCO Precis Oncol"},{"issue":"8","key":"815_CR39","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/S1470-2045(10)70130-3","volume":"11","author":"W De Roock","year":"2010","unstructured":"De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11(8):753\u201362. https:\/\/doi.org\/10.1016\/S1470-2045(10)70130-3.","journal-title":"Lancet Oncol"},{"issue":"12","key":"815_CR40","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1093\/oncolo\/oyae259","volume":"29","author":"F Yasin","year":"2024","unstructured":"Yasin F, Sokol E, Vasan N, Pavlick DC, Huang RSP, Pelletier M, et al. Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations. Oncologist. 2024;29(12):1059\u201367. https:\/\/doi.org\/10.1093\/oncolo\/oyae259.","journal-title":"Oncologist"},{"issue":"2","key":"815_CR41","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.bbcan.2015.03.005","volume":"1855","author":"S Turajlic","year":"2015","unstructured":"Turajlic S, McGranahan N, Swanton C. Inferring mutational timing and reconstructing tumour evolutionary histories. Biochim Biophys Acta. 2015;1855(2):264\u201375. https:\/\/doi.org\/10.1016\/j.bbcan.2015.03.005.","journal-title":"Biochim Biophys Acta"},{"issue":"8","key":"815_CR42","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1186\/s13059-014-0454-7","volume":"15","author":"AR Brannon","year":"2014","unstructured":"Brannon AR, Vakiani E, Sylvester BE, Scott SN, McDermott G, Shah RH, et al. Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol. 2014;15(8):454. https:\/\/doi.org\/10.1186\/s13059-014-0454-7.","journal-title":"Genome Biol"},{"issue":"3","key":"815_CR43","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1158\/1078-0432.CCR-14-3081","volume":"22","author":"O Arqu\u00e9s","year":"2016","unstructured":"Arqu\u00e9s O, Chicote I, Puig I, Tenbaum SP, Argil\u00e9s G, Dienstmann R, et al. Tankyrase inhibition blocks Wnt\/\u03b2-catenin pathway and reverts resistance to PI3K and AKT inhibitors in the treatment of colorectal cancer. Clin Cancer Res. 2016;22(3):644\u201356. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-3081.","journal-title":"Clin Cancer Res"},{"issue":"3","key":"815_CR44","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1080\/14728222.2024.2331015","volume":"28","author":"PA Yakkala","year":"2024","unstructured":"Yakkala PA, Naaz F, Shafi S, Kamal A. PI3K and tankyrase inhibitors as therapeutic targets in colorectal cancer. Expert Opin Ther Targets. 2024;28(3):159\u201377. https:\/\/doi.org\/10.1080\/14728222.2024.2331015.","journal-title":"Expert Opin Ther Targets"},{"issue":"12","key":"815_CR45","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.bbadis.2008.06.007","volume":"1782","author":"IA Voutsadakis","year":"2008","unstructured":"Voutsadakis IA. The ubiquitin-proteasome system in colorectal cancer. Biochim Biophys Acta. 2008;1782(12):800\u20138. https:\/\/doi.org\/10.1016\/j.bbadis.2008.06.007.","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"815_CR46","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.jcmgh.2020.04.007","volume":"10","author":"A Prossomariti","year":"2020","unstructured":"Prossomariti A, Piazzi G, Alquati C, Ricciardiello L. Are Wnt\/\u03b2-catenin and PI3K\/AKT\/mTORC1 distinct pathways in colorectal cancer? Cell Mol Gastroenterol Hepatol. 2020;10(3):491\u2013506. https:\/\/doi.org\/10.1016\/j.jcmgh.2020.04.007.","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"1","key":"815_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms24010001","volume":"24","author":"MP Pinto","year":"2022","unstructured":"Pinto MP, Mu\u00f1oz-Medel M, Retamal IN, Bravo M, Latapiat V, C\u00f3rdova-Delgado M, et al. Differentially expressed genes and signaling pathways potentially involved in primary resistance to chemo-immunotherapy in advanced-stage gastric cancer patients. Int J Mol Sci. 2022;24(1):1. https:\/\/doi.org\/10.3390\/ijms24010001.","journal-title":"Int J Mol Sci"},{"issue":"11","key":"815_CR48","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1016\/j.cell.2022.04.013","volume":"185","author":"S Battaglioni","year":"2022","unstructured":"Battaglioni S, Benjamin D, W\u00e4lchli M, Maier T, Hall MN. mTOR substrate phosphorylation in growth control. Cell. 2022;185(11):1814\u201336. https:\/\/doi.org\/10.1016\/j.cell.2022.04.013.","journal-title":"Cell"},{"issue":"6","key":"815_CR49","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1007\/s11523-017-0530-5","volume":"12","author":"ZA Wainberg","year":"2017","unstructured":"Wainberg ZA, Alsina M, Soares HP, Bra\u00f1a I, Britten CD, Del Conte G, et al. A multi-arm phase I study of the PI3K\/mTOR inhibitors PF-04691502 and gedatolisib (PF-05212384) plus irinotecan or the MEK Inhibitor PD-0325901 in advanced cancer. Target Oncol. 2017;12(6):775\u201385. https:\/\/doi.org\/10.1007\/s11523-017-0530-5.","journal-title":"Target Oncol"},{"issue":"19","key":"815_CR50","doi-asserted-by":"publisher","first-page":"5981","DOI":"10.1158\/1078-0432.CCR-17-0725","volume":"23","author":"J Mateo","year":"2017","unstructured":"Mateo J, Ganji G, Lemech C, Burris HA, Han SW, Swales K, et al. A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2017;23(19):5981\u201392. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-0725.","journal-title":"Clin Cancer Res"},{"issue":"2","key":"815_CR51","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.soc.2021.11.006","volume":"31","author":"S Sakata","year":"2022","unstructured":"Sakata S, Larson DW. Targeted therapy for colorectal cancer. Surg Oncol Clin N Am. 2022;31(2):255\u201364. https:\/\/doi.org\/10.1016\/j.soc.2021.11.006.","journal-title":"Surg Oncol Clin N Am"},{"issue":"24","key":"815_CR52","doi-asserted-by":"publisher","first-page":"13264","DOI":"10.3390\/ijms252413264","volume":"25","author":"R Aslam","year":"2024","unstructured":"Aslam R, Richards CE, Fay J, Hudson L, Workman J, Lee CL, et al. Synergistic effects of the combination of alpelisib (PI3K inhibitor) and ribociclib (CDK4\/6 inhibitor) in preclinical colorectal cancer models. Int J Mol Sci. 2024;25(24):13264. https:\/\/doi.org\/10.3390\/ijms252413264.","journal-title":"Int J Mol Sci"},{"issue":"9","key":"815_CR53","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.3390\/cancers12092500","volume":"12","author":"HJ Lee","year":"2020","unstructured":"Lee HJ, Kim KJ, Sung JH, Nam M, Suh KJ, Kim JW, et al. PI3K p110\u03b1 blockade enhances anti-tumor efficacy of abemaciclib in human colorectal cancer cells. Cancers (Basel). 2020;12(9):2500. https:\/\/doi.org\/10.3390\/cancers12092500.","journal-title":"Cancers (Basel)"},{"issue":"42","key":"815_CR54","doi-asserted-by":"publisher","first-page":"68546","DOI":"10.18632\/oncotarget.11843","volume":"7","author":"MS Fernandes","year":"2016","unstructured":"Fernandes MS, Melo S, Velho S, Carneiro P, Carneiro F, Seruca R. Specific inhibition of p110\u03b1 subunit of PI3K: putative therapeutic strategy for KRAS mutant colorectal cancers. Oncotarget. 2016;7(42):68546\u201358. https:\/\/doi.org\/10.18632\/oncotarget.11843.","journal-title":"Oncotarget"},{"issue":"7","key":"815_CR55","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1158\/2159-8290.CD-24-0614","volume":"15","author":"M Marasco","year":"2025","unstructured":"Marasco M, Kumar D, Garcia Borrego S, Seale T, Maddalena G, Mezzadra R, et al. Direct inhibition of RAS reveals the features of oncogenic signaling driven by RAS G12 and Q61 mutations. Cancer Discov. 2025;15(7):1392\u2013409. https:\/\/doi.org\/10.1158\/2159-8290.CD-24-0614.","journal-title":"Cancer Discov"},{"key":"815_CR56","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-24-0995","author":"KW Song","year":"2025","unstructured":"Song KW, Ong CC, Lin E, Lau J, Sodir NM, Jin DX, et al. KRAS codon-specific mutations differentially toggle PI3K pathway signaling and alter sensitivity to inavolisib (GDC-0077). Mol Cancer Ther. 2025. https:\/\/doi.org\/10.1158\/1535-7163.MCT-24-0995.","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"815_CR57","doi-asserted-by":"publisher","first-page":"2223388","DOI":"10.1080\/15384047.2023.2223388","volume":"24","author":"CL Lee","year":"2023","unstructured":"Lee CL, Cremona M, Farrelly A, Workman JA, Kennedy S, Aslam R, et al. Preclinical evaluation of the CDK4\/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer. Cancer Biol Ther. 2023;24(1):2223388. https:\/\/doi.org\/10.1080\/15384047.2023.2223388.","journal-title":"Cancer Biol Ther"},{"issue":"1","key":"815_CR58","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12935-021-01800-7","volume":"21","author":"C Liu","year":"2021","unstructured":"Liu C, Xing W, Yu H, Zhang W, Si T. ABCB1 and ABCG2 restricts the efficacy of gedatolisib (PF-05212384), a PI3K inhibitor in colorectal cancer cells. Cancer Cell Int. 2021;21(1):108. https:\/\/doi.org\/10.1186\/s12935-021-01800-7.","journal-title":"Cancer Cell Int"},{"issue":"2","key":"815_CR59","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1002\/ijc.31662","volume":"144","author":"YL Park","year":"2019","unstructured":"Park YL, Kim HP, Cho YW, Min DW, Cheon SK, Lim YJ, et al. Activation of WNT\/\u03b2-catenin signaling results in resistance to a dual PI3K\/mTOR inhibitor in colorectal cancer cells harboring PIK3CA mutations. Int J Cancer. 2019;144(2):389\u2013401. https:\/\/doi.org\/10.1002\/ijc.31662.","journal-title":"Int J Cancer"},{"key":"815_CR60","doi-asserted-by":"publisher","first-page":"1002295","DOI":"10.37349\/etat.2025.1002295","volume":"6","author":"IA Voutsadakis","year":"2025","unstructured":"Voutsadakis IA. Genomic alterations in the WNT\/\u03b2-catenin pathway and resistance of colorectal cancer cells to pathway-targeting therapies. Explor Target Antitumor Ther. 2025;6:1002295. https:\/\/doi.org\/10.37349\/etat.2025.1002295.","journal-title":"Explor Target Antitumor Ther"},{"issue":"8","key":"815_CR61","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.32604\/or.2024.051653","volume":"32","author":"G Hamilton","year":"2024","unstructured":"Hamilton G, Eggerstorfer MT, Stickler S. Development of PROTACS degrading KRAS and SOS1. Oncol Res. 2024;32(8):1257\u201364. https:\/\/doi.org\/10.32604\/or.2024.051653.","journal-title":"Oncol Res"},{"key":"815_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217112","volume":"598","author":"H Zhang","year":"2024","unstructured":"Zhang H, Zhang L, He Y, Jiang D, Sun J, Luo Q, et al. PI3K PROTAC overcomes the lapatinib resistance in PIK3CA-mutant HER2 positive breast cancer. Cancer Lett. 2024;598:217112. https:\/\/doi.org\/10.1016\/j.canlet.2024.217112.","journal-title":"Cancer Lett"},{"key":"815_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2022.116707","volume":"61","author":"H Wang","year":"2022","unstructured":"Wang H, Li C, Liu X, Ma M. Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase. Bioorg Med Chem. 2022;61:116707. https:\/\/doi.org\/10.1016\/j.bmc.2022.116707.","journal-title":"Bioorg Med Chem"},{"issue":"7719","key":"815_CR64","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41586-018-0343-4","volume":"560","author":"BD Hopkins","year":"2018","unstructured":"Hopkins BD, Pauli C, Du X, Wang DG, Li X, Wu D, et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018;560(7719):499\u2013503. https:\/\/doi.org\/10.1038\/s41586-018-0343-4.","journal-title":"Nature"},{"issue":"1","key":"815_CR65","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s12664-018-0923-0","volume":"38","author":"M Reed","year":"2019","unstructured":"Reed M, Patrick C, Croft B, Walde N, Voutsadakis IA. The metabolic syndrome and its components as prognostic factors in metastatic colorectal cancer. Indian J Gastroenterol. 2019;38(1):15\u201322. https:\/\/doi.org\/10.1007\/s12664-018-0923-0.","journal-title":"Indian J Gastroenterol"},{"issue":"2","key":"815_CR66","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1093\/ajcn\/nqy093","volume":"108","author":"FK Tabung","year":"2018","unstructured":"Tabung FK, Wang W, Fung TT, Smith-Warner SA, Keum N, Wu K, et al. Association of dietary insulinemic potential and colorectal cancer risk in men and women. Am J Clin Nutr. 2018;108(2):363\u201370. https:\/\/doi.org\/10.1093\/ajcn\/nqy093.","journal-title":"Am J Clin Nutr"},{"issue":"11","key":"815_CR67","doi-asserted-by":"publisher","first-page":"4311","DOI":"10.1172\/JCI57909","volume":"121","author":"H Ebi","year":"2011","unstructured":"Ebi H, Corcoran RB, Singh A, Chen Z, Song Y, Lifshits E, et al. Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers. J Clin Invest. 2011;121(11):4311\u201321. https:\/\/doi.org\/10.1172\/JCI57909.","journal-title":"J Clin Invest"},{"issue":"6","key":"815_CR68","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","volume":"168","author":"RA Saxton","year":"2017","unstructured":"Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168(6):960\u201376. https:\/\/doi.org\/10.1016\/j.cell.2017.02.004.","journal-title":"Cell"},{"issue":"46","key":"815_CR69","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1038\/s41388-024-03170-6","volume":"43","author":"R Bordone","year":"2024","unstructured":"Bordone R, Ivy DM, D\u2019Amico R, Barba M, Gaggianesi M, Di Pastena F, et al. MYC upstream region orchestrates resistance to PI3K inhibitors in cancer cells through FOXO3a-mediated autophagic adaptation. Oncogene. 2024;43(46):3349\u201365. https:\/\/doi.org\/10.1038\/s41388-024-03170-6.","journal-title":"Oncogene"},{"issue":"4","key":"815_CR70","doi-asserted-by":"publisher","first-page":"6608","DOI":"10.18632\/oncotarget.14245","volume":"8","author":"HJ Kim","year":"2017","unstructured":"Kim HJ, Lee SY, Kim CY, Kim YH, Ju W, Kim SC. Subcellular localization of FOXO3a as a potential biomarker of response to combined treatment with inhibitors of PI3K and autophagy in PIK3CA-mutant cancer cells. Oncotarget. 2017;8(4):6608\u201322. https:\/\/doi.org\/10.18632\/oncotarget.14245.","journal-title":"Oncotarget"},{"key":"815_CR71","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101170","volume":"78","author":"X Niu","year":"2025","unstructured":"Niu X, You Q, Hou K, Tian Y, Wei P, Zhu Y, et al. Autophagy in cancer development, immune evasion, and drug resistance. Drug Resist Updat. 2025;78:101170. https:\/\/doi.org\/10.1016\/j.drup.2024.101170.","journal-title":"Drug Resist Updat"},{"key":"815_CR72","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19671","volume":"6","author":"JM Mulcahy Levy","year":"2017","unstructured":"Mulcahy Levy JM, Zahedi S, Griesinger AM, Morin A, Davies KD, Aisner DL, et al. Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors. Elife. 2017;6:e19671. https:\/\/doi.org\/10.7554\/eLife.19671.","journal-title":"Elife"},{"issue":"6","key":"815_CR73","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.cell.2013.08.015","volume":"154","author":"Y Wei","year":"2013","unstructured":"Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, et al. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell. 2013;154(6):1269\u201384. https:\/\/doi.org\/10.1016\/j.cell.2013.08.015.","journal-title":"Cell"},{"issue":"1","key":"815_CR74","doi-asserted-by":"publisher","first-page":"1956173","DOI":"10.1080\/2162402X.2021.1956173","volume":"10","author":"T Ugai","year":"2021","unstructured":"Ugai T, Zhao M, Shimizu T, Akimoto N, Shi S, Takashima Y, et al. Association of PIK3CA mutation and PTEN loss with expression of CD274 (PD-L1) in colorectal carcinoma. Oncoimmunology. 2021;10(1):1956173. https:\/\/doi.org\/10.1080\/2162402X.2021.1956173.","journal-title":"Oncoimmunology"},{"issue":"12","key":"815_CR75","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1158\/1541-7786.MCR-19-0545","volume":"17","author":"S Chandrasekaran","year":"2019","unstructured":"Chandrasekaran S, Sasaki M, Scharer CD, Kissick HT, Patterson DG, Magliocca KR, et al. Phosphoinositide 3-kinase signaling can modulate MHC class I and II expression. Mol Cancer Res. 2019;17(12):2395\u2013409. https:\/\/doi.org\/10.1158\/1541-7786.MCR-19-0545.","journal-title":"Mol Cancer Res"},{"issue":"1","key":"815_CR76","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s40425-019-0627-8","volume":"7","author":"KA Marijt","year":"2019","unstructured":"Marijt KA, Sluijter M, Blijleven L, Tolmeijer SH, Scheeren FA, van der Burg SH, et al. Metabolic stress in cancer cells induces immune escape through a PI3K-dependent blockade of IFN\u03b3 receptor signaling. J Immunother Cancer. 2019;7(1):152. https:\/\/doi.org\/10.1186\/s40425-019-0627-8.","journal-title":"J Immunother Cancer"},{"key":"815_CR77","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-00663","author":"S Wedam","year":"2025","unstructured":"Wedam S, Narayan P, Gittleman H, Cheng J, Bhatnagar V, Sabit H, et al. US Food and Drug administration approval summary: inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer. J Clin Oncol. 2025. https:\/\/doi.org\/10.1200\/JCO-25-00663.","journal-title":"J Clin Oncol"},{"issue":"2","key":"815_CR78","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1056\/NEJMoa2501796","volume":"393","author":"KL Jhaveri","year":"2025","unstructured":"Jhaveri KL, Im SA, Saura C, Loibl S, Kalinsky K, Schmid P, et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. N Engl J Med. 2025;393(2):151\u201361. https:\/\/doi.org\/10.1056\/NEJMoa2501796.","journal-title":"N Engl J Med"},{"issue":"12","key":"815_CR79","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1691\/ph.2021.1820","volume":"76","author":"M Zhu","year":"2021","unstructured":"Zhu M, Jin Q, Xin Y. Recent clinical advances in PI3K inhibitors on colorectal cancer. Pharmazie. 2021;76(12):568\u201373. https:\/\/doi.org\/10.1691\/ph.2021.1820.","journal-title":"Pharmazie"},{"issue":"5","key":"815_CR80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038033","volume":"7","author":"I Garrido-Laguna","year":"2012","unstructured":"Garrido-Laguna I, Hong DS, Janku F, Nguyen LM, Falchook GS, Fu S, et al. KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors. PLoS ONE. 2012;7(5):e38033. https:\/\/doi.org\/10.1371\/journal.pone.0038033.","journal-title":"PLoS ONE"},{"issue":"1","key":"815_CR81","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/s41698-025-00975-w","volume":"9","author":"A Milsap","year":"2025","unstructured":"Milsap A, Tsai J, Jafry B, Kim A, Ali Kazmi SM, Verma N. Comprehensive analysis of PIK3CA mutations in advanced colorectal cancer using circulating tumor DNA profiling. NPJ Precis Oncol. 2025;9(1):220. https:\/\/doi.org\/10.1038\/s41698-025-00975-w.","journal-title":"NPJ Precis Oncol"},{"issue":"5","key":"815_CR82","doi-asserted-by":"publisher","first-page":"533","DOI":"10.21873\/cgp.20470","volume":"21","author":"IA Voutsadakis","year":"2024","unstructured":"Voutsadakis IA. PIK3CA mutated colorectal cancers without KRAS, NRAS and BRAF mutations possess common and potentially targetable mutations in epigenetic modifiers and DNA damage response genes. Cancer Genom Proteom. 2024;21(5):533\u201348. https:\/\/doi.org\/10.21873\/cgp.20470.","journal-title":"Cancer Genom Proteom"},{"issue":"17","key":"815_CR83","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1158\/1078-0432.CCR-24-0967","volume":"30","author":"SS Sk\u00e5nland","year":"2024","unstructured":"Sk\u00e5nland SS, Okkenhaug K, Davids MS. PI3K inhibitors in hematology: when one door closes\u2026. Clin Cancer Res. 2024;30(17):3667\u201375. https:\/\/doi.org\/10.1158\/1078-0432.CCR-24-0967.","journal-title":"Clin Cancer Res"}],"container-title":["Molecular Diagnosis & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-025-00815-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40291-025-00815-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40291-025-00815-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:52:28Z","timestamp":1769496748000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40291-025-00815-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":83,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["815"],"URL":"https:\/\/doi.org\/10.1007\/s40291-025-00815-4","relation":{},"ISSN":["1177-1062","1179-2000"],"issn-type":[{"value":"1177-1062","type":"print"},{"value":"1179-2000","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"8 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"IAV declares no conflicts of interest related to this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"No supplemental data beyond the data described in the article are available.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}