{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:17:40Z","timestamp":1787944660687,"version":"build-2784847793"},"reference-count":155,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"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>PIK3CA, which encodes the p110\u03b1 catalytic subunit of phosphoinositide 3-kinase (PI3K), is one of the most frequently altered oncogenes in human cancer and a major driver of tumor initiation, progression, metastasis, and therapeutic resistance. Over the past two decades, advances in structural biology, cancer genomics, and translational research have substantially expanded our understanding of PIK3CA function and established the PI3K pathway as a clinically actionable therapeutic target. This review provides an overview of the structural organization and physiological functions of the PI3K\u03b1 complex, the molecular mechanisms underlying oncogenic activation, and the diverse spectrum of PIK3CA alterations across human malignancies. We also summarize the current landscape of PI3K-targeted therapies, highlighting both approved agents and emerging therapeutic strategies. Clinical evidence supports the rational integration of PI3K inhibitors with endocrine therapy, CDK4\/6 inhibitors, MAPK pathway inhibitors, dual PI3K\/mTOR inhibition, and immune checkpoint blockade. In addition, accumulating evidence indicates that PIK3CA plays a pivotal role in shaping the tumor immune microenvironment, providing a biological rationale for combining PI3K inhibition with immunotherapy. Finally, we discuss future directions in precision oncology, emphasizing integrated molecular profiling, liquid biopsy, single-cell and spatial technologies, functional genomics, and evolutionary approaches as complementary strategies to refine patient selection, overcome therapeutic resistance, and optimize clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers18172798","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"2798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PIK3CA in Cancer: Structure, Biology, Alterations, and Actionability"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-3855","authenticated-orcid":false,"given":"Alessandro","family":"Ottaiano","sequence":"first","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-0056","authenticated-orcid":false,"given":"Carmine","family":"Picone","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Science, \u201cVincenzo Tiberio\u201d University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Santorsola","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9837-9148","authenticated-orcid":false,"given":"Massimiliano","family":"Berretta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Cutolo","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6252-573X","authenticated-orcid":false,"given":"Andrea","family":"Belli","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3093-5408","authenticated-orcid":false,"given":"Francesco","family":"Izzo","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Di Carluccio","sequence":"additional","affiliation":[{"name":"Department of Economics, University of Foggia, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniello","family":"Acampora","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Tarotto","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3295-840X","authenticated-orcid":false,"given":"Salvatore","family":"Stilo","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Correra","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-1883","authenticated-orcid":false,"given":"Maurizio","family":"Capuozzo","sequence":"additional","affiliation":[{"name":"Pharmaceutical Department, Asl Napoli 3 Sud, Via Marittima 3, 80056 Ercolano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Carrat\u00f9","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2408-6091","authenticated-orcid":false,"given":"Michele","family":"Caraglia","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Nasti","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5274-3989","authenticated-orcid":false,"given":"Giovanni","family":"Savarese","sequence":"additional","affiliation":[{"name":"Centro AMES, Via Padre Carmine Fico 24, 80013 Casalnuovo di Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","first-page":"18292","article-title":"Oncogenic mutations of PIK3CA in human cancers","volume":"101","author":"Samuels","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1158\/1535-7163.MCT-10-0994","article-title":"PIK3CA mutations in patients with advanced cancers treated with PI3K\/AKT\/mTOR axis inhibitors","volume":"10","author":"Janku","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1158\/0008-5472.CAN-12-1726","article-title":"PIK3CA mutation H1047R is associated with response to PI3K\/AKT\/mTOR signaling pathway inhibitors in early-phase clinical trials","volume":"73","author":"Janku","year":"2013","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100934","DOI":"10.1016\/j.jbior.2022.100934","article-title":"The mutational profiles and corresponding therapeutic implications of PI3K mutations in cancer","volume":"87","author":"Nazarenko","year":"2023","journal-title":"Adv. Biol. Regul."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12943-024-02072-1","article-title":"Targeting PI3K family with small-molecule inhibitors in cancer therapy: Current clinical status and future directions","volume":"23","author":"Li","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101430","DOI":"10.1016\/j.gendis.2024.101430","article-title":"Oncogenic activation of PIK3CA in cancers: Emerging targeted therapies in precision oncology","volume":"12","author":"Wang","year":"2025","journal-title":"Genes Dis."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41573-022-00582-5","article-title":"Beyond PI3Ks: Targeting phosphoinositide kinases in disease","volume":"22","author":"Burke","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sheng, Z., Beck, P., Gabby, M., Habte-Mariam, S., and Mitkos, K. (2024). Molecular Basis of Oncogenic PI3K Proteins. Cancers, 17.","DOI":"10.3390\/cancers17010077"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1146\/annurev-pharmtox-082924-022724","article-title":"Structural Insights into the Development of Inhibitors Against Cancer-Specific Mutations of PI3K\u03b1","volume":"66","author":"Liu","year":"2026","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB signaling: Navigating downstream","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1177\/1758834014530023","article-title":"The PI3K\/AKT\/mTOR pathway in breast cancer: Targets, trials and biomarkers","volume":"6","author":"Paplomata","year":"2014","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1146\/annurev-genom-121222-114518","article-title":"PIK3CA-Related Disorders: From Disease Mechanism to Evidence-Based Treatments","volume":"25","author":"Morin","year":"2024","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nri1056","article-title":"PI3K in lymphocyte development, differentiation and activation","volume":"3","author":"Okkenhaug","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1126\/science.275.5308.1943","article-title":"PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer","volume":"275","author":"Li","year":"1997","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cancergen.2025.08.010","article-title":"Comprehensive analysis of oncogenic determinants across tumor types via multi-omics integration","volume":"298-299","author":"Ubaid","year":"2025","journal-title":"Cancer Genet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4467","DOI":"10.1038\/s41598-023-31593-w","article-title":"PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy","volume":"13","author":"Tharin","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1158\/1078-0432.CCR-22-2270","article-title":"Genetic Heterogeneity and Tissue-specific Patterns of Tumors with Multiple PIK3CA Mutations","volume":"29","author":"Sivakumar","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.gim.2022.01.001","article-title":"Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC)","volume":"24","author":"Horak","year":"2022","journal-title":"Genet Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13073-018-0531-8","article-title":"Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations","volume":"10","author":"Tamborero","year":"2018","journal-title":"Genome Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e150335","DOI":"10.1172\/JCI150335","article-title":"Therapeutic implications of activating noncanonical PIK3CA mutations in head and neck squamous cell carcinoma","volume":"131","author":"Jin","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1158\/1078-0432.CCR-22-2115","article-title":"Biology and Targetability of the Extended Spectrum of PIK3CA Mutations Detected in Breast Carcinoma","volume":"29","author":"Rugo","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1158\/1078-0432.CCR-25-4018","article-title":"The Pan-Tumor Landscape of Gene Amplifications and Copy Number Amplification Ratio for Established and Emerging Clinical Targets","volume":"32","author":"Lee","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1136\/ijgc-2024-005295","article-title":"Copy number variations in endometrial cancer: From biological significance to clinical utility","volume":"34","author":"Dugo","year":"2024","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.4143\/crt.2021.963","article-title":"Genomic Correlates of Unfavorable Outcome in Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemoradiation","volume":"54","author":"Wei","year":"2022","journal-title":"Cancer Res. Treat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1200\/JCO.2026.44.16_suppl.1036","article-title":"Prognostic impact of PIK3CA amplifications and co-occurring mutations detected through circulating tumor DNA (ctDNA) in metastatic breast cancer (MBC)","volume":"44","author":"Foffano","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_28","first-page":"3","article-title":"Comprehensive study of gene fusions in sarcomas","volume":"43","author":"Chen","year":"2025","journal-title":"Investig. New Drugs"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, H., Tang, R., Jiang, L., and Jia, Y. (2024). The role of PIK3CA gene mutations in colorectal cancer and the selection of treatment strategies. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1494802"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: The Catalogue of Somatic Mutations in Cancer","volume":"47","author":"Tate","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13058-020-01284-9","article-title":"Frequency and spectrum of PIK3CA somatic mutations in breast cancer","volume":"22","author":"Chic","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chao, T.C., Tsai, Y.F., Liu, C.Y., Lien, P.J., Lin, Y.S., Feng, C.J., Chen, Y.J., Lai, J.I., Hsu, C.Y., and Lynn, J.J. (2023). Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: A retrospective next-generation sequencing database analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1192946"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100843","DOI":"10.1016\/j.currproblcancer.2022.100843","article-title":"Comparison of mutational profiles between triple-negative and hormone receptor-positive\/human epidermal growth factor receptor 2-negative breast cancers in T2N0-1M0 stage: Implications of TP53 and PIK3CA mutations in Korean early-stage breast cancers","volume":"46","author":"Lee","year":"2022","journal-title":"Curr. Probl. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102140","DOI":"10.1016\/j.tranon.2024.102140","article-title":"The PIK3CA gene and its pivotal role in tumor tropism of triple-negative breast cancer","volume":"50","author":"Mallick","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"x3","DOI":"10.1093\/annonc\/mdz281","article-title":"Overview of the relevance of PI3K pathway in HR-positive breast cancer","volume":"30","author":"Vasan","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"188847","DOI":"10.1016\/j.bbcan.2022.188847","article-title":"Predictive and prognostic value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors: A systematic review and meta-analysis","volume":"1878","author":"Shi","year":"2023","journal-title":"Bio-Chim. Biophys. Acta Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1200\/JCO.2017.74.8301","article-title":"Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data","volume":"36","author":"Zardavas","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fillbrunn, M., Signorovitch, J., Andr\u00e9, F., Wang, I., Lorenzo, I., Ridolfi, A., Park, J., Dua, A., and Rugo, H.S. (2022). PIK3CA mutation status, progression and survival in advanced HR+\/HER2- breast cancer: A meta-analysis of published clinical trials. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10078-5"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6064","DOI":"10.1158\/1078-0432.CCR-07-0266","article-title":"Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas","volume":"13","author":"Barbareschi","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhu, K., Wu, Y., He, P., Fan, Y., Zhong, X., Zheng, H., and Luo, T. (2022). PI3K\/AKT\/mTOR-Targeted Therapy for Breast Cancer. Cells, 11.","DOI":"10.3390\/cells11162508"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","article-title":"Alpelisib for PIK3CA-Mutated, Hormone Receptor\u2013Positive Advanced Breast Cancer","volume":"380","author":"Ciruelos","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1373\/clinchem.2013.205740","article-title":"The emerging genomic landscape of endometrial cancer","volume":"60","author":"Bell","year":"2014","journal-title":"Clin. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network, and Levine, D.A. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497, 67\u201373.","DOI":"10.1038\/nature12113"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1158\/0008-5472.CAN-05-2620","article-title":"High frequency of coexistent PIK3CA mutations and PTEN loss in endometrial carcinoma","volume":"65","author":"Oda","year":"2005","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Niu, S., Molberg, K., Castrillon, D.H., Lucas, E., and Chen, H. (2024). Biomarkers in the Diagnosis of Endometrial Precancers. Mo-lecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions. Cancers, 16.","DOI":"10.3390\/cancers16061159"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bredin, H.K., Krakstad, C., and Hoivik, E.A. (2023). PIK3CA mutations and their impact on survival outcomes of patients with endometrial cancer: A systematic review and meta-analysis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0283203"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ygyno.2013.11.015","article-title":"PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma","volume":"132","author":"McIntyre","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10240","DOI":"10.1038\/s41598-017-10717-z","article-title":"PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer","volume":"7","author":"Mjos","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Voutsadakis, I.A. (2021). PI3KCA Mutations in Uterine Cervix Carcinoma. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020220"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Medda, A., Duca, D., and Chiocca, S. (2021). Human Papillomavirus and Cellular Pathways: Hits and Targets. Pathogens, 10.","DOI":"10.3390\/pathogens10030262"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13045-018-0674-5","article-title":"The PIK3CA E542K and E545K mutations promote glycolysis and proliferation via induction of the \u03b2-catenin\/SIRT3 signaling pathway in cervical cancer","volume":"11","author":"Jiang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100786","DOI":"10.1016\/j.tranon.2020.100786","article-title":"Tumor Location Is Associated with the Prevalence of Braf and Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan","volume":"13","author":"Taniguchi","year":"2020","journal-title":"Transl. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1038\/s41598-024-55139-w","article-title":"Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients","volume":"14","author":"Ciepiela","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Leite, L.F., Noronha, M.M., de Menezes, J.S.A., da Concei\u00e7\u00e3o, L.D., Almeida, L.F.C., Cappellaro, A.P., Belotto, M., Biachi de Castria, T., Peixoto, R.D., and Megid, T.B.C. (2025). Anti-EGFR Therapy in Metastatic Colorectal Cancer: Identifying, Tracking, and Overcoming Resistance. Cancers, 17.","DOI":"10.3390\/cancers17172804"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Voutsadakis, I.A. (Mol. Diagn. Ther., 2025). From PIK3CA mutations to rational PI3K inhibition for the treatment of colorectal cancer, Mol. Diagn. Ther., online ahead of print.","DOI":"10.1007\/s40291-025-00815-4"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s11523-022-00898-7","article-title":"Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer","volume":"17","author":"Tan","year":"2022","journal-title":"Target Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1158\/1078-0432.CCR-11-2410","article-title":"Prognostic role of PIK3CA mutation in colorectal cancer: Cohort study and literature review","volume":"18","author":"Liao","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s13402-011-0054-4","article-title":"PIK3CA kinase domain mutation identifies a subgroup of stage III colon cancer patients with poor prognosis","volume":"34","author":"Sarasqueta","year":"2011","journal-title":"Cell. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1001\/jamaoto.2013.3210","article-title":"High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer","volume":"139","author":"Nichols","year":"2013","journal-title":"JAMA Otolaryngol. Head. Neck Surg."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cochicho, D., Esteves, S., Rito, M., Silva, F., Martins, L., Montalv\u00e3o, P., Cunha, M., Magalh\u00e3es, M., Gil da Costa, R.M., and Felix, A. (2022). PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival. Cancers, 14.","DOI":"10.3390\/cancers14051286"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s41199-018-0030-z","article-title":"Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC)","volume":"3","author":"Jung","year":"2018","journal-title":"Cancers Head Neck"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rossi, S., Pagliaro, A., Masini, S., Finocchiaro, G., Toschi, L., Bria, E., Antonio, V., Alessio, S., Inno, A., and Gori, S. (2026). PIK3CA Alterations in NSCLC: Clinical Characteristics of a \u201cNeglected\u201d Population of Oncogene-Addicted Patients. Biomedicines, 14.","DOI":"10.3390\/biomedicines14020362"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41571-025-01085-z","article-title":"Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC\u2014Mechanisms and evolving treatment approaches","volume":"23","author":"Zhao","year":"2026","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.18632\/oncotarget.2834","article-title":"PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies","volume":"6","author":"Scheffler","year":"2015","journal-title":"Oncotarget"},{"key":"ref_67","first-page":"3189","article-title":"Survival and prognosis analyses of concurrent PIK3CA mutations in EGFR mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors","volume":"11","author":"Qiu","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.lungcan.2016.11.018","article-title":"PIK3CA mutations as prognostic factor in squamous cell lung carcinoma","volume":"103","author":"McGowan","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1007\/s11033-026-12215-w","article-title":"Emerging molecular targets in gynaecologic cancers: Clinical implications for personalized therapy","volume":"53","author":"Shaik","year":"2026","journal-title":"Mol. Biol. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/j.humpath.2012.03.011","article-title":"Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma","volume":"43","author":"Rahman","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_71","first-page":"9","article-title":"Prognostic impact of molecular profiles and molecular signatures in clear cell ovarian cancer","volume":"278","author":"Hein","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/his.15555","article-title":"Molecular pathology of bladder cancer","volume":"88","author":"Blanca","year":"2026","journal-title":"Histopathology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.urolonc.2018.10.015","article-title":"Mutational landscape of non-muscle-invasive bladder cancer","volume":"40","author":"Hurst","year":"2022","journal-title":"Urol. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Tom\u00e1s, A., and Pojo, M. (2025). PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115276"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/ctm2.32","article-title":"Classification of gastric cancer by EBV status combined with molecular profiling predicts patient prognosis","volume":"10","author":"Miaozhen","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Raith, F., O\u2019Donovan, D.H., Lemos, C., Politz, O., and Haendler, B. (2023). Addressing the Reciprocal Crosstalk between the AR and the PI3K\/AKT\/mTOR Signaling Pathways for Prostate Cancer Treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032289"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7651","DOI":"10.18632\/oncotarget.23871","article-title":"Association between PIK3CA alteration and prognosis of gastric cancer patients: A meta-analysis","volume":"9","author":"Li","year":"2018","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Mustafa, M., Ahmad, R., Tantry, I.Q., Ahmad, W., Siddiqui, S., Alam, M., Abbas, K., Hassan, M.I., and Habib, S. (2024). Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications. Cells, 13.","DOI":"10.3390\/cells13221838"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"189083","DOI":"10.1016\/j.bbcan.2024.189083","article-title":"Mechanistic regulation of FOXO transcription factors in the nucleus","volume":"1879","author":"Guo","year":"2024","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.tips.2022.09.010","article-title":"FOXO transcription factors as therapeutic targets in human diseases","volume":"43","author":"Paik","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s43556-026-00411-w","article-title":"Tumor cell cycle regulation: Integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies","volume":"7","author":"Wan","year":"2026","journal-title":"Mol. Biomed."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e202208103","DOI":"10.1083\/jcb.202208103","article-title":"MTORC1 beyond anabolic metabolism: Regulation of cell death","volume":"221","author":"Zhu","year":"2022","journal-title":"J. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.7150\/ijbs.89942","article-title":"The PI3K\/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer","volume":"20","author":"Fontana","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cmet.2022.01.007","article-title":"The hallmarks of cancer metabolism: Still emerging","volume":"34","author":"Pavlova","year":"2022","journal-title":"Cell Metab."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Karar, J., and Maity, A. (2011). PI3K\/AKT\/mTOR Pathway in Angiogenesis. Front. Mol. Neurosci., 4.","DOI":"10.3389\/fnmol.2011.00051"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.canlet.2017.06.035","article-title":"Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery","volume":"403","author":"Kim","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Wolosowicz, M., Prokopiuk, S., and Kaminski, T.W. (2024). The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413691"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e003402","DOI":"10.1136\/jitc-2021-003402","article-title":"PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment","volume":"10","author":"Collins","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41573-026-01388-5","article-title":"A renaissance in targeting the PI3K\/AKT\/mTOR pathway","volume":"25","author":"Conduit","year":"2026","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Sun, E.J., Wankell, M., Palamuthusingam, P., McFarlane, C., and Hebbard, L. (2021). Targeting the PI3K\/Akt\/mTOR Pathway in Hepatocellular Carcinoma. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111639"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1002\/mco2.124","article-title":"STAT3 pathway in cancers: Past, present, and future","volume":"3","author":"Wang","year":"2022","journal-title":"MedComm"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Mafi, S., Mansoori, B., Taeb, S., Sadeghi, H., Abbasi, R., Cho, W.C., and Rostamzadeh, D. (2022). MTOR-Mediated Regulation of Immune Responses in Cancer and Tumor Microenvironment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.774103"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.7150\/jca.77619","article-title":"Clinical implications of the interaction between PD-1\/PD-L1 and PI3K\/AKT\/mTOR pathway in progression and treatment of non-small cell lung cancer","volume":"13","author":"Quan","year":"2022","journal-title":"J. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/imm.13682","article-title":"Targeting PI3K\u03b1 increases the efficacy of anti-PD-1 antibody in cervical cancer","volume":"170","author":"Jiang","year":"2023","journal-title":"Immunology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3892\/ol.2024.14700","article-title":"PI3K\/AKT\/mTOR and PD 1\/CTLA 4\/CD28 pathways as key targets of cancer immunotherapy","volume":"28","author":"Wang","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1200\/JCO.2022.40.16_suppl.5052","article-title":"Phase I\/II study of the selective PI3K\u03b2 inhibitor GSK2636771 in combination with pembrolizumab in patients with metastatic castration-resistant prostate cancer and PTEN loss","volume":"40","author":"Dumbrava","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"gag163","DOI":"10.1093\/pnasnexus\/pgag163","article-title":"Oncogenic PIK3CA mutations shape an immunoregulatory microenvironment in mosaic overgrowth disorders","volume":"5","author":"Galasso","year":"2026","journal-title":"PNAS Nexus"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Nico\u015b, M., and Krawczyk, P. (2022). Genetic Clonality as the Hallmark Driving Evolution of Non-Small Cell Lung Cancer. Cancers, 14.","DOI":"10.3390\/cancers14071813"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"djw036","DOI":"10.1093\/jnci\/djw036","article-title":"The Conundrum of Genetic \u201cDrivers\u201d in Benign Conditions","volume":"108","author":"Kato","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41571-022-00633-1","article-title":"At a crossroads: How to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy","volume":"19","author":"Vasan","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41698-022-00334-z","article-title":"Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors","volume":"6","author":"Lee","year":"2022","journal-title":"npj Precis. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Khatpe, A.S., Adebayo, A.K., Herodotou, C.A., Kumar, B., and Nakshatri, H. (2021). Nexus between PI3K\/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13030369"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/10799893.2023.2187643","article-title":"Estrogen receptors as potential therapeutic target in endometrial cancer","volume":"43","author":"Guha","year":"2023","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Koulouris, A., Tsagkaris, C., Corriero, A.C., Metro, G., and Mountzios, G. (2022). Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies. Cancers, 14.","DOI":"10.3390\/cancers14143337"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.lungcan.2022.05.011","article-title":"Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies","volume":"170","author":"Johnson","year":"2022","journal-title":"Lung Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zhong, H., Zhou, Z., Wang, H., Wang, R., Shen, K., Huang, R., and Wang, Z. (2024). The Biological Roles and Clinical Applications of the PI3K\/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413376"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/onc.2012.53","article-title":"Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations","volume":"32","author":"Yuan","year":"2013","journal-title":"Oncogene"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1158\/0008-5472.CAN-10-0738","article-title":"Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation","volume":"71","author":"Adams","year":"2011","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ydbio.2015.04.022","article-title":"Heterozygous expression of the oncogenic Pik3ca(H1047R) mutation during murine development results in fatal embryonic and extraembryonic defects","volume":"404","author":"Hare","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Reske, J.J., Wilson, M.R., Holladay, J., Siwicki, R.A., Skalski, H., Harkins, S., Adams, M., Risinger, J.I., Hostetter, G., and Lin, K. (2021). Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009986"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/path.4645","article-title":"Mouse models of intestinal cancer","volume":"238","author":"Jackstadt","year":"2016","journal-title":"J. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s12072-021-10237-z","article-title":"Application of CRISPR-Cas9 based gene editing to study the pathogenesis of colon and liver cancer using organoids","volume":"15","author":"Ramakrishna","year":"2021","journal-title":"Hepatol. Int."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.1158\/1078-0432.CCR-19-1627","article-title":"Generation of Genetically Engineered Mouse Lung Organoid Models for Squamous Cell Lung Cancers Allows for the Study of Combinatorial Immunotherapy","volume":"26","author":"Hai","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41392-023-01419-2","article-title":"Patient-derived xenograft models in cancer therapy: Technologies and applications","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s43018-021-00218-4","article-title":"The present and future of PI3K inhibitors for cancer therapy","volume":"2","author":"Castel","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Li, H., Prever, L., Hirsch, E., and Gulluni, F. (2021). Targeting PI3K\/AKT\/mTOR Signaling Pathway in Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13143517"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1097\/JTO.0000000000000183","article-title":"A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic non-small-cell lung cancer","volume":"9","author":"Levy","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.oraloncology.2014.12.013","article-title":"A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer","volume":"51","author":"Jimeno","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/annonc\/mdu574","article-title":"A randomized, phase II trial of cetuximab with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer","volume":"26","author":"Jimeno","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1097\/JTO.0000000000000607","article-title":"Safety and efficacy of buparlisib (BKM120) in patients with PI3K pathway-activated non-small cell lung cancer: Results from the phase II BASALT-1 study","volume":"10","author":"Vansteenkiste","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_121","first-page":"1270","article-title":"Phase II study of PX-866 in recurrent glioblastoma","volume":"17","author":"Pitz","year":"2015","journal-title":"Neuro Oncol."},{"key":"ref_122","first-page":"337","article-title":"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","volume":"15","author":"Bowles","year":"2016","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.1158\/1078-0432.CCR-18-0613","article-title":"Phase II study of taselisib (GDC-0032) in combination with fulvestrant in patients with HER2-negative, hormone receptor-positive advanced breast cancer","volume":"24","author":"Dickler","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1158\/1078-0432.CCR-16-2888","article-title":"A first-in-human, phase I, dose-escalation study of TAK-117, a selective PI3K\u03b1 isoform inhibitor, in patients with advanced solid malignancies","volume":"23","author":"Juric","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1093\/oncolo\/oyac192","article-title":"Randomized Phase II Trial of Sapanisertib \u00b1 TAK-117 vs. Everolimus in Patients with Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy","volume":"27","author":"Choueiri","year":"2022","journal-title":"Oncologist"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ygyno.2023.09.013","article-title":"A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer","volume":"178","author":"Han","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1056\/NEJMoa2404625","article-title":"Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer","volume":"391","author":"Turner","year":"2024","journal-title":"N Engl. J. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.annonc.2020.10.596","article-title":"Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: The SANDPIPER trial","volume":"32","author":"Dent","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e2100424","DOI":"10.1200\/PO.21.00424","article-title":"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","volume":"6","author":"Krop","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/j.jtho.2019.05.029","article-title":"SWOG S1400B (NCT02785913), a phase II study of GDC-0032 (taselisib) for previously treated PI3K-positive patients with stage IV squamous cell lung cancer (Lung-MAP sub-study)","volume":"14","author":"Langer","year":"2019","journal-title":"J. Thorac. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"108004","DOI":"10.1016\/j.oraloncology.2026.108004","article-title":"Efficacy of buparlisib according to PIK3CA mutation status in recurrent or metastatic head and neck squamous cell carcinoma: A multicenter phase II trial","volume":"178","author":"Gauduchon","year":"2026","journal-title":"Oral Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1200\/JCO-25-02643","article-title":"VIKTORIA-1 Study Group. VIKTORIA-1 trial of gedatolisib plus fulvestrant with or without palbociclib in hormone receptor-positive\/HER2-negative\/PIK3CA wild-type advanced breast cancer","volume":"44","author":"Hurvitz","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1158\/2159-8290.CD-21-1696","article-title":"Alpelisib monotherapy for PI3K-altered, pretreated advanced breast cancer: A phase II study","volume":"12","author":"Savas","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/S1470-2045(19)30334-1","article-title":"Neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with oestrogen receptor-positive, HER2-negative, early-stage breast cancer (LORELEI): A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"20","author":"Saura","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e629","DOI":"10.1016\/S1470-2045(24)00673-9","article-title":"Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4\/6 inhibitor (BYLieve): One cohort of a phase 2, multicentre, open-label, non-comparative study","volume":"25","author":"Rugo","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1200\/JCO-25-00225","article-title":"Primary analysis of EPIK-O\/ENGOT-ov61: Alpelisib plus olaparib versus chemotherapy in platinum-resistant or platinum-refractory high-grade serous ovarian cancer without BRCA mutation","volume":"43","author":"Konstantinopoulos","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1158\/1078-0432.CCR-25-2833","article-title":"PI3K inhibition in combination with tamoxifen in patients with metastatic HR-positive\/HER2-negative breast cancer: Clinical and circulating tumor DNA results","volume":"32","author":"Voorthuis","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.clgc.2019.03.005","article-title":"A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration-resistant Prostate Cancer: Canadian Cancer Trials Group Study IND205","volume":"17","author":"Hotte","year":"2019","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3390\/jmp2030022","article-title":"Liquid Biopsy for Biomarker Testing in Non-Small Cell Lung Cancer: A European Perspective","volume":"2","author":"Malapelle","year":"2021","journal-title":"J. Mol. Pathol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Di Mauro, A., Berretta, M., Santorsola, M., Ferrara, G., Picone, C., Savarese, G., and Ottaiano, A. (2025). Towards Post-Genomic Oncology: Embracing Cancer Complexity via Artificial Intelligence, Multi-Targeted Therapeutics, Drug Repurposing, and Innovative Study Designs. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26167723"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Ottaiano, A., Ianniello, M., Santorsola, M., Ruggiero, R., Sirica, R., Sabbatino, F., Perri, F., Cascella, M., Di Marzo, M., and Berretta, M. (2023). From Chaos to Opportunity: Decoding Cancer Heterogeneity for Enhanced Treatment Strategies. Biology, 12.","DOI":"10.3390\/biology12091183"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ccr.2010.10.031","article-title":"AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity","volume":"19","author":"Chandarlapaty","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1038\/onc.2010.626","article-title":"PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer","volume":"30","author":"Serra","year":"2011","journal-title":"Oncogene"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nature13948","article-title":"Convergent loss of PTEN leads to clinical resistance to a PI(3)K\u03b1 inhibitor","volume":"518","author":"Juric","year":"2015","journal-title":"Nature"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s43018-020-0047-1","article-title":"Alterations in PTEN and ESR1 promote clinical resistance to alpelisib plus aromatase inhibitors","volume":"1","author":"Razavi","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/2159-8290.CD-23-0704","article-title":"Allosteric PI3K\u03b1 Inhibition Overcomes On-target Resistance to Orthosteric Inhibitors Mediated by Secondary PIK3CA Mutations","volume":"14","author":"Varkaris","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1158\/2159-8290.CD-16-0305","article-title":"Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer","volume":"6","author":"Le","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-025-02180-4","article-title":"Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs","volume":"10","author":"Gremke","year":"2025","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41523-026-00968-3","article-title":"Expert recommendations for PIK3CA testing in HR+\/HER2- locally advanced and metastatic breast cancer","volume":"12","author":"Rojo","year":"2026","journal-title":"npj Breast Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"17082","DOI":"10.1038\/s41598-020-74086-w","article-title":"PIK3CA mutation enrichment and quantitation from blood and tissue","volume":"10","author":"Keraite","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.annonc.2022.05.520","article-title":"ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: A report from the ESMO Precision Medicine Working Group","volume":"33","author":"Pascual","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1038\/ng.3391","article-title":"In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer","volume":"47","author":"Janiszewska","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1158\/2159-8290.CD-20-1265","article-title":"Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer","volume":"12","author":"Chang","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1158\/2159-8290.CD-23-0944","article-title":"Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3K\u03b1 Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia","volume":"14","author":"Varkaris","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1056\/NEJMoa2214131","article-title":"CAPItello-291 Study Group. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer","volume":"388","author":"Turner","year":"2023","journal-title":"N Engl. J. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2798\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:38:44Z","timestamp":1787942324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":155,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172798"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172798","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}