{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:13:39Z","timestamp":1789506819267,"version":"build-2803163510"},"reference-count":129,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003287","name":"Rally Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001512","name":"National Brain Tumor Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001512","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001794","name":"Pediatric Brain Tumor Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007886","name":"Dana-Farber Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016610","name":"Andrew McDonough B+ Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ejcancer.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Cancer"],"published-print":{"date-parts":[[2024,8]]},"DOI":"10.1016\/j.ejca.2024.114145","type":"journal-article","created":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T12:39:53Z","timestamp":1717850393000},"page":"114145","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Paediatric strategy forum for medicinal product development of PI3-K, mTOR, AKT and GSK3\u03b2 inhibitors in children and adolescents with cancer"],"prefix":"10.1016","volume":"207","author":[{"given":"Andrew DJ","family":"Pearson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"DuBois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Macy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"de Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Donoghue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Knoderer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Bernardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickie","family":"Buenger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Canaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Cantley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Friend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Glade-Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Gorbatchevsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Gore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas S.","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejan","family":"Juric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh Anna","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Leach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Liaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Lesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Ligas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Ludwinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynley","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"McDonough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Nysom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ours","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Pappo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.William","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Rosenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Scobie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Weigel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Weinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Karres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Vassal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejca.2024.114145_bib1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrd4204","article-title":"PI3K and cancer: lessons, challenges and opportunities","volume":"13","author":"Fruman","year":"2014","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.ejca.2024.114145_bib2","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nrd2926","article-title":"Targeting the phosphoinositide 3-kinase pathway in cancer","volume":"8","author":"Liu","year":"2009","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.ejca.2024.114145_bib3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nrclinonc.2018.28","article-title":"Targeting the PI3K pathway in cancer: are we making headway?","volume":"15","author":"Janku","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib4","unstructured":"Combination Chemotherapy With or Without Temsirolimus in Treating Patients with Intermediate Risk Rhabdomyosarcoma. https:\/\/clinicaltrials.gov\/study\/NCT02567435. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib5","unstructured":"Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC) (EXIST-1). \u3008https:\/\/clinicaltrials.gov\/study\/NCT00789828\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib6","unstructured":"Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication (BIOMEDE). \u3008https:\/\/www.clinicaltrials.gov\/study\/NCT02233049\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib8","unstructured":"ACCELERATE, EMA: Report: Paediatric strategy forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies, May 2017; http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Report\/2017\/06\/WC500228940.pdf. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib9","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejca.2019.01.013","article-title":"ACCELERATE and European Medicine Agency Paediatric Strategy Forum for medicinal product development for mature B-cell malignancies in children","volume":"110","author":"Pearson","year":"2019","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib10","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ejca.2019.12.029","article-title":"ACCELERATE and European Medicines Agency Paediatric Strategy Forum for Medicinal Product Development of checkpoint inhibitors for use in combination therapy in paediatric patients","volume":"127","author":"Pearson","year":"2020","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejca.2020.04.038","article-title":"Paediatric strategy forum for medicinal product development for acute myeloid leukaemia in children and adolescents","volume":"136","author":"Pearson","year":"2020","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ejca.2020.08.014","article-title":"Paediatric strategy forum for medicinal product development of epigenetic modifiers for children: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration","volume":"139","author":"Pearson","year":"2020","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib13","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejca.2021.08.022","article-title":"Second Paediatric Strategy Forum for anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies ACCELERATE in collaboration with the European Medicines Agency with the participation of the Food and Drug Administration","volume":"157","author":"Pearson","year":"2021","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ejca.2021.10.016","article-title":"Paediatric Strategy Forum for medicinal product development of chimeric antigen receptor T-cells in children and adolescents with cancer: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration","volume":"160","author":"Pearson","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ejca.2022.06.008","article-title":"Paediatric Strategy Forum for medicinal product development of multi-targeted kinase inhibitors in bone sarcomas: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration","volume":"173","author":"Pearson","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ejca.2022.09.036","article-title":"Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration","volume":"177","author":"Pearson","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2023.112950","volume":"190","author":"Pearson","year":"2023","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib18","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejca.2014.10.029","article-title":"Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer","volume":"51","author":"Vassal","year":"2015","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib19","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejca.2022.01.033","article-title":"ACCELERATE - Five years accelerating cancer drug development for children and adolescents","volume":"166","author":"Pearson","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib20","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/332644a0","article-title":"Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate","volume":"332","author":"Whitman","year":"1988","journal-title":"Nature"},{"key":"10.1016\/j.ejca.2024.114145_bib21","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/ng0497-356","article-title":"Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers","volume":"15","author":"Steck","year":"1997","journal-title":"Nat Genet"},{"key":"10.1016\/j.ejca.2024.114145_bib22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ccr.2005.05.014","article-title":"Mutant PIK3CA promotes cell growth and invasion of human cancer cells","volume":"7","author":"Samuels","year":"2005","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib23","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.ejca.2024.114145_bib24","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1001\/jamaoncol.2016.0891","article-title":"Landscape of Phosphatidylinositol-3-Kinase Pathway Alterations Across 19784 Diverse Solid Tumors.","volume":"2","author":"Millis","year":"2016","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib25","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.ajhg.2012.05.006","article-title":"Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome","volume":"90","author":"Kurek","year":"2012","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.ejca.2024.114145_bib26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrm2882","article-title":"The emerging mechanisms of isoform-specific PI3K signalling","volume":"11","author":"Vanhaesebroeck","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.ejca.2024.114145_bib27","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":"10.1016\/j.ejca.2024.114145_bib28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tibs.2005.02.008","article-title":"Signalling by PI3K isoforms: insights from gene-targeted mice","volume":"30","author":"Vanhaesebroeck","year":"2005","journal-title":"Trends Biochem"},{"key":"10.1016\/j.ejca.2024.114145_bib29","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1242\/jcs.113.2.207","article-title":"The PI 3-kinase isoforms p110(alpha) and p110(beta) have differential roles in PDGF- and insulin-mediated signaling.","volume":"113","author":"Hooshmand-Rad","year":"2000","journal-title":"J Cell Sci"},{"key":"10.1016\/j.ejca.2024.114145_bib30","doi-asserted-by":"crossref","first-page":"956","DOI":"10.3390\/jcm12030956","article-title":"Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex-Current Views on Their Pathogenesis and Management","volume":"12","author":"Gao","year":"2023","journal-title":"J Clin Med"},{"key":"10.1016\/j.ejca.2024.114145_bib31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41586-018-0343-4","article-title":"Suppression of insulin feedback enhances the efficacy of PI3K inhibitors","volume":"560","author":"Hopkins","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ejca.2024.114145_bib32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1158\/1078-0432.CCR-16-0134","article-title":"A Phase Ib Study of Alpelisib (BYL719), a PI3K\u03b1-Specific Inhibitor, with Letrozole in ER+\/HER2- Metastatic Breast Cancer","volume":"23","author":"Mayer","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"13_Supplement","key":"10.1016\/j.ejca.2024.114145_bib33","doi-asserted-by":"crossref","first-page":"CT046","DOI":"10.1158\/1538-7445.AM2018-CT046","article-title":"A phase I basket study of the PI3K inhibitor taselisib (GDC-0032) in PIK3CA-mutated locally advanced or metastatic solid tumors","volume":"78","author":"Jhaveri","year":"2018","journal-title":"Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib34","unstructured":"Klippel A. et al Presented at 2021 AACR-NCI-EORTC, Oct 7\u201311, Boston Massachusetts."},{"key":"10.1016\/j.ejca.2024.114145_bib35","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1055\/s-0035-1564440","article-title":"Overgrowth Syndromes","volume":"4","author":"Edmondson","year":"2015","journal-title":"J Pedia Genet"},{"key":"10.1016\/j.ejca.2024.114145_bib36","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/ng.2332","article-title":"Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA","volume":"44","author":"Lindhurst","year":"2012","journal-title":"Nat Genet"},{"key":"10.1016\/j.ejca.2024.114145_bib37","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1002\/ajmg.a.32023","article-title":"Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients","volume":"143A","author":"Sapp","year":"2007","journal-title":"Am J Med Genet A"},{"issue":"2","key":"10.1016\/j.ejca.2024.114145_bib38","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/ajmg.a.36836","article-title":"PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation","volume":"167A","author":"Keppler-Noreuil","year":"2015","journal-title":"Am J Med Genet A"},{"key":"10.1016\/j.ejca.2024.114145_bib39","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41586-018-0217-9","article-title":"Targeted therapy in patients with PIK3CA-related overgrowth syndrome","volume":"558","author":"Venot","year":"2018","journal-title":"Nature"},{"issue":"614","key":"10.1016\/j.ejca.2024.114145_bib40","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abg0809","article-title":"Alpelisib administration reduced lymphatic malformations in a mouse model and in patients","volume":"13","author":"Delestre","year":"2021","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.ejca.2024.114145_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.gim.2023.100969","article-title":"Alpelisib for treatment of patients with PIK3CA-Related Overgrowth Spectrum (PROS)","author":"Canaud","year":"2023","journal-title":"Genet Med"},{"key":"10.1016\/j.ejca.2024.114145_bib42","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1200\/JCO.2017.72.7107","article-title":"Phosphatidylinositol 3-Kinase \u03b1-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: results from the first-in-human study","volume":"36","author":"Juric","year":"2018","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib43","unstructured":"FDA approves alpelisib for PIK3CA-related overgrowth spectrum https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-alpelisib-pik3ca-related-overgrowth-spectrum. (Accessed 19 November 2023)."},{"issue":"3","key":"10.1016\/j.ejca.2024.114145_bib44","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20212148","article-title":"Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib","volume":"219","author":"Morin","year":"2022","journal-title":"J Exp Med"},{"key":"10.1016\/j.ejca.2024.114145_bib45","unstructured":"Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (EPIK-P2). https:\/\/clinicaltrials.gov\/study\/NCT04589650."},{"key":"10.1016\/j.ejca.2024.114145_bib46","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.ade7823","article-title":"PIK3CA gain-of-function mutation in adipose tissue induces metabolic reprogramming with Warburg-like effect and severe endocrine disruption","volume":"8","author":"Ladraa","year":"2022","journal-title":"Sci Adv"},{"key":"10.1016\/j.ejca.2024.114145_bib47","doi-asserted-by":"crossref","unstructured":"Delestre F., Venot Q., Bayard C., Fraissenon A., Ladraa S., Hoguin et al. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med.;13eabg0809. doi: 10.1126\/scitranslmed.abg0809.","DOI":"10.1126\/scitranslmed.abg0809"},{"key":"10.1016\/j.ejca.2024.114145_bib48","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1056\/NEJMoa1104017","article-title":"A mosaic activating mutation in AKT1 associated with the Proteus syndrome","volume":"365","author":"Lindhurst","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ejca.2024.114145_bib49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/BF00661895","article-title":"The proteus syndrome. Partial gigantism of the hands and\/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections","volume":"140","author":"Wiedemann","year":"1983","journal-title":"Eur J Pedia"},{"key":"10.1016\/j.ejca.2024.114145_bib50","doi-asserted-by":"crossref","first-page":"6455","DOI":"10.1021\/acs.jmedchem.6b00619","article-title":"Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): an Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor","volume":"59","author":"Lapierre","year":"2016","journal-title":"J Med Chem"},{"key":"10.1016\/j.ejca.2024.114145_bib51","doi-asserted-by":"crossref","DOI":"10.1038\/srep17162","article-title":"Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome","volume":"5","author":"Lindhurst","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.ejca.2024.114145_bib52","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ajhg.2019.01.015","article-title":"Pharmacodynamic Study of Miransertib in Individuals with Proteus Syndrome","volume":"104","author":"Keppler-Noreuil","year":"2019","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.ejca.2024.114145_bib53","unstructured":"MK-7075 (Miransertib) in Proteus Syndrome. \u3008https:\/\/clinicaltrials.gov\/study\/NCT04316546\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib54","doi-asserted-by":"crossref","first-page":"10992","DOI":"10.1158\/0008-5472.CAN-05-2612","article-title":"Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells","volume":"65","author":"Isakoff","year":"2005","journal-title":"Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib55","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nm.2402","article-title":"Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms","volume":"17","author":"Liu","year":"2011","journal-title":"Nat Med"},{"key":"10.1016\/j.ejca.2024.114145_bib56","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1172\/JCI59309","article-title":"An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice","volume":"122","author":"Kinross","year":"2012","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ejca.2024.114145_bib57","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1126\/science.aaw9032","article-title":"Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3K\u03b1 inhibitors","volume":"366","author":"Vasan","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.ejca.2024.114145_bib58","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1126\/science.1073560","article-title":"Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice","volume":"297","author":"Okkenhaug","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.ejca.2024.114145_bib59","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1053\/j.gastro.2010.07.008","article-title":"Altered macrophage function contributes to colitis in mice defective in the phosphoinositide-3 kinase subunit p110\u03b4","volume":"139","author":"Uno","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejca.2024.114145_bib60","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1158\/1535-7163.MCT-13-0865","article-title":"Characterization of the novel and specific PI3K\u03b1 inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials","volume":"13","author":"Fritsch","year":"2014","journal-title":"Mol Cancer Ther"},{"issue":"5_Supplement","key":"10.1016\/j.ejca.2024.114145_bib61","article-title":"Differential Gene Mutation Landscape in Patients With PIK3CA-altered and Non-altered Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer in the SOLAR-1 Clinical Study","volume":"83","author":"Juric","year":"2023","journal-title":"Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib62","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa4442","article-title":"PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer","volume":"7","author":"Bosch","year":"2015","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.ejca.2024.114145_bib63","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2018.4475","article-title":"Alpelisib plus Fulvestrant in PIK3CA-Altered and PIK3CA-Wild-Type Estrogen Receptor-Positive Advanced Breast Cancer: a phase 1b Clinical Trial","volume":"5","author":"Juric","year":"2019","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib64","doi-asserted-by":"crossref","unstructured":"Andr\u00e9 F. Ciruelos E. Rubovszky G., et al. Alpelisib + fulvestrant for HR+, HER2\u2212 advanced breast cancer: Results of the phase III SOLAR-1 trial. Presented at European Society for Medical Oncology; October 19\u201323, 2018; Munich, Germany, Abstract LBA3.","DOI":"10.1093\/annonc\/mdy424.010"},{"key":"10.1016\/j.ejca.2024.114145_bib65","doi-asserted-by":"crossref","DOI":"10.1186\/bcr2419","article-title":"PD 0332991, a selective cyclin D kinase 4\/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro","volume":"11","author":"Finn","year":"2009","journal-title":"Breast Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib66","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1158\/1078-0432.CCR-14-0816","article-title":"Molecular Pathways: targeting the Cyclin D-CDK4\/6 Axis for Cancer Treatment","volume":"21","author":"VanArsdale","year":"2015","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib67","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":"10.1016\/j.ejca.2024.114145_bib68","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1158\/2159-8290.CD-18-0830","article-title":"PTEN Loss Mediates Clinical Cross-Resistance to CDK4\/6 and PI3K\u03b1 Inhibitors in Breast Cancer","volume":"10","author":"Costa","year":"2020","journal-title":"Cancer Discov"},{"key":"10.1016\/j.ejca.2024.114145_bib69","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ccr.2014.05.020","article-title":"CDK 4\/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors","volume":"26","author":"Vora","year":"2014","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib70","unstructured":"First-in-Human Study of Mutant-selective PI3K\u03b1 Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination with Fulvestrant in Patients with Advanced Breast Cancer. https:\/\/clinicaltrials.gov\/study\/NCT05216432. (Accessed 19 November 2023)."},{"issue":"16_suppl","key":"10.1016\/j.ejca.2024.114145_bib73","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1200\/JCO.2022.40.16_suppl.1005","volume":"40","author":"Jones","year":"2022","journal-title":"J Clin Oncol"},{"issue":"suppl_4","key":"10.1016\/j.ejca.2024.114145_bib74","first-page":"S348","article-title":"A phase III trial of capivasertib and fulvestrant versus placebo and fulvestrant in patients with HR+\/HER2\u2212 breast cancer (CAPItello-291)","volume":"31","author":"Turner","year":"2020","journal-title":"Ann Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib75","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrclinonc.2014.40","article-title":"Determining the optimal dose in the development of anticancer agents","volume":"11","author":"Mathijssen","year":"2014","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib76","unstructured":"Catalogue Of Somatic Mutations In Cancer (COSMIC).\u3008https:\/\/cancer.sanger.ac.uk\/cosmic\u3009. (Accessed 19 November 2023)."},{"issue":"D1","key":"10.1016\/j.ejca.2024.114145_bib77","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":"10.1016\/j.ejca.2024.114145_bib78","unstructured":"cBioPortal. https:\/\/www.cbioportal.org. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib79","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"10.1016\/j.ejca.2024.114145_bib80","unstructured":"PeCan St Judes Cloud. https:\/\/pecan.stjude.cloud. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib81","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ccell.2017.08.017","article-title":"Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma","volume":"32","author":"Mackay","year":"2017","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib82","unstructured":"Samotolisib in Treating Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K\/MTOR Mutations (A Pediatric MATCH Treatment Trial). \u3008https:\/\/clinicaltrials.gov\/study\/NCT03213678\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib85","doi-asserted-by":"crossref","first-page":"219","DOI":"10.31083\/j.fbl2707219","article-title":"The \"SEED\" Study: the feasibility of selecting patient-specific biologically targeted therapy with sorafenib, everolimus, erlotinib or dasatinib for pediatric and young adult patients with recurrent or refractory brain tumors","volume":"27","author":"Cole","year":"2022","journal-title":"Front Biosci (Landmark Ed"},{"issue":"2","key":"10.1016\/j.ejca.2024.114145_bib86","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.28787","article-title":"A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma","volume":"68","author":"Wright","year":"2021","journal-title":"Pedia Blood Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib87","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1093\/neuonc\/noaa071","article-title":"A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1-associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study","volume":"22","author":"Ullrich","year":"2020","journal-title":"Neuro Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib88","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/neuonc\/not150","article-title":"Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas","volume":"16","author":"Karajannis","year":"2014","journal-title":"Neuro Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib89","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1158\/1078-0432.CCR-20-4078","article-title":"A phase i and surgical study of ribociclib and everolimus in children with recurrent or refractory malignant brain tumors: a pediatric brain tumor consortium study","volume":"27","author":"DeWire","year":"2021","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib90","article-title":"Phase I study of ribociclib and everolimus in children with newly diagnosed DIPG and high-grade glioma: A CONNECT pediatric neuro-oncology consortium report","volume":"4","author":"DeWire","year":"2022","journal-title":"Neurooncol Adv"},{"key":"10.1016\/j.ejca.2024.114145_bib91","first-page":"1515","article-title":"The effect of everolimus on subependymal giant cell astrocytoma (SEGA) in children with tuberous sclerosis complex","author":"Bakhtiary","year":"2021","journal-title":"Iran J Child Neurol"},{"key":"10.1016\/j.ejca.2024.114145_bib92","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","article-title":"Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial","volume":"381","author":"Franz","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.ejca.2024.114145_bib93","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1200\/JCO.2007.11.4017","article-title":"Phase I study of everolimus in pediatric patients with refractory solid tumors","volume":"25","author":"Fouladi","year":"2007","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib94","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1007\/s10637-013-0028-7","article-title":"Multicenter phase II study of everolimus in patients with metastatic or recurrent bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide","volume":"31","author":"Yoo","year":"2013","journal-title":"Invest N Drugs"},{"key":"10.1016\/j.ejca.2024.114145_bib95","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1002\/cncr.32722","article-title":"A phase 1 trial of everolimus and bevacizumab in children with recurrent solid tumors","volume":"126","author":"Santana","year":"2020","journal-title":"Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib96","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.27062","article-title":"Phase I trial of the mTOR inhibitor everolimus in combination with multi-agent chemotherapy in relapsed childhood acute lymphoblastic leukemia","volume":"65","author":"Place","year":"2018","journal-title":"Pedia Blood Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib97","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1158\/1078-0432.CCR-20-1215","article-title":"Safety and efficacy of vorinostat plus sirolimus or everolimus in patients with relapsed refractory hodgkin lymphoma","volume":"26","author":"Janku","year":"2020","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib98","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1200\/JCO.21.01152","article-title":"Phase I or II Study of Ribociclib in Combination with Topotecan-Temozolomide or Everolimus in Children With Advanced Malignancies: Arms A and B of the AcS\u00e9-ESMART Trial","volume":"39","author":"Bautista","year":"2021","journal-title":"J Clin Oncol"},{"issue":"2","key":"10.1016\/j.ejca.2024.114145_bib99","doi-asserted-by":"crossref","DOI":"10.1200\/PO.18.00189","article-title":"Phase I Study of the BRAF Inhibitor Vemurafenib in Combination With the Mammalian Target of Rapamycin Inhibitor Everolimus in Patients With BRAF-Mutated Malignancies","author":"Subbiah","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib100","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41588-021-00819-w","article-title":"A first-generation pediatric cancer dependency map","volume":"53","author":"Dharia","year":"2021","journal-title":"Nat Genet"},{"key":"10.1016\/j.ejca.2024.114145_bib101","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/pbc.24874","article-title":"Phase 1 trial of temsirolimus in combination with irinotecan and temozolomide in children, adolescents and young adults with relapsed or refractory solid tumors: a Children's Oncology Group Study","volume":"61","author":"Bagatell","year":"2014","journal-title":"Pedia Blood Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib102","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1200\/JCO.19.00576","article-title":"Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: a report from the children's oncology group","volume":"37","author":"Mascarenhas","year":"2019","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib103","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/S1470-2045(17)30355-8","article-title":"Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial","volume":"18","author":"Mody","year":"2017","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib104","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ejca.2021.08.010","article-title":"First-in-child phase I\/II study of the dual mTORC1\/2 inhibitor vistusertib (AZD2014) as monotherapy and in combination with topotecan-temozolomide in children with advanced malignancies: arms E and F of the AcS\u00e9-ESMART trial","volume":"157","author":"Morscher","year":"2021","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib105","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.3324\/haematol.2021.279520","article-title":"Temsirolimus combined with cyclophosphamide and etoposide for pediatric patients with relapsed\/refractory acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia consortium trial (TACL 2014-001)","volume":"107","author":"Tasian","year":"2022","journal-title":"Haematologica"},{"issue":"15_suppl","key":"10.1016\/j.ejca.2024.114145_bib107","doi-asserted-by":"crossref","first-page":"10527","DOI":"10.1200\/JCO.2020.38.15_suppl.10527","article-title":"A phase I\/II study of lenvatinib (LEN) plus everolimus (EVE) in recurrent and refractory pediatric solid tumors, including CNS tumors","volume":"38","author":"Dela Cruz","year":"2020","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib108","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S1470-2045(14)71136-2","article-title":"Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial","volume":"16","author":"Grignani","year":"2015","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib109","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/annonc\/mdr151","article-title":"A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study","volume":"23","author":"Grignani","year":"2012","journal-title":"Ann Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib110","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1200\/JCO.2015.65.5381","article-title":"Outcome of patients with recurrent osteosarcoma enrolled in seven phase ii trials through children's cancer group, pediatric oncology group, and children's oncology group: learning from the past to move forward clinical trial","volume":"34","author":"Lagmay","year":"2016","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib111","doi-asserted-by":"crossref","first-page":"23851","DOI":"10.18632\/oncotarget.12904","article-title":"Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors","volume":"8","author":"Vo","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejca.2024.114145_bib112","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.28134","article-title":"A phase I study of sirolimus in combination with metronomic therapy (CHOAnome) in children with recurrent or refractory solid and brain tumors","volume":"67","author":"Qayed","year":"2020","journal-title":"Pedia Blood Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib113","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1158\/1078-0432.CCR-12-0061","article-title":"Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors","volume":"18","author":"Naing","year":"2012","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib114","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1470-2045(13)70049-4","article-title":"Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial","volume":"14","author":"Schwartz","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib115","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/pbc.25334","article-title":"Phase II study of cixutumumab in combination with temsirolimus in pediatric patient and young adults with recurrent or refractory sarcoma: a report from the Children's Oncology Group","volume":"62","author":"Wagner","year":"2015","journal-title":"Pedia Blood Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib116","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.26409","article-title":"A phase I study of perifosine with temsirolimus for recurrent pediatric solid tumors","volume":"64","author":"Becher","year":"2017","journal-title":"Pedia Blood Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib117","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/annonc\/mdu482","article-title":"A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors","volume":"26","author":"Tolcher","year":"2015","journal-title":"Ann Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib123","doi-asserted-by":"crossref","DOI":"10.1136\/esmoopen-2020-000871","article-title":"Evaluation of the contribution of randomised cancer clinical trials evaluating agents without documented single-agent activity","volume":"5","author":"Foster","year":"2020","journal-title":"ESMO Open"},{"key":"10.1016\/j.ejca.2024.114145_bib124","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.cell.2017.11.009","article-title":"Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy","volume":"171","author":"Palmer","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib125","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1177\/1740774519873883","article-title":"Benefit, burden, and impact for a cohort of post-approval cancer combination trials","volume":"17","author":"Carlisle","year":"2020","journal-title":"Clin Trials"},{"key":"10.1016\/j.ejca.2024.114145_bib126","first-page":"OF1","article-title":"ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma","author":"Jackson","year":"2023","journal-title":"Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib127","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.ccell.2023.03.007","article-title":"Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities","volume":"41","author":"Sun","year":"2023","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib128","doi-asserted-by":"crossref","first-page":"57525","DOI":"10.18632\/oncotarget.10544","article-title":"Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors","volume":"7","author":"Vaughan","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejca.2024.114145_bib129","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.devcel.2005.07.014","article-title":"The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors","volume":"9","author":"Sjostrom","year":"2005","journal-title":"Dev Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib130","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ccr.2008.12.005","article-title":"Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma","volume":"15","author":"Otto","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejca.2024.114145_bib131","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1158\/0008-5472.CAN-06-2201","article-title":"Activation of Akt predicts poor outcome in neuroblastoma","volume":"67","author":"Opel","year":"2007","journal-title":"Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib132","doi-asserted-by":"crossref","first-page":"8139","DOI":"10.1158\/0008-5472.CAN-05-2769","article-title":"Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma","volume":"66","author":"Chesler","year":"2006","journal-title":"Cancer Res"},{"key":"10.1016\/j.ejca.2024.114145_bib133","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejca.2022.09.025","article-title":"European regulatory strategy for supporting childhood cancer therapy developments","volume":"177","author":"Karres","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ejca.2024.114145_bib134","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1200\/JCO.20.02152","article-title":"Accelerating the global development of pediatric cancer drugs: a call to coordinate the submissions of pediatric investigation plans and pediatric study plans to the European Medicines Agency and US Food and Drug Administration","volume":"38","author":"Reaman","year":"2020","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2024.114145_bib135","unstructured":"Common Commentary - EMA\/FDA Common issues requested for discussion by the respective agency (EMA\/PDCO and FDA) concerning paediatric oncology development plans (Paediatric Investigation Plans [PIPs] and initial Pediatric Study Plans [iPSPs]). \u3008https:\/\/www.fda.gov\/media\/147197\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib136","unstructured":"Common Commentary - EMA\/FDA Common issues requested for discussion by the respective agency (EMA\/PDCO and FDA) concerning paediatric oncology development plans (Paediatric Investigation Plans [PIPs] and initial Pediatric Study Plans [iPSPs]). \u3008https:\/\/www.ema.europa.eu\/en\/documents\/other\/common-commentary-ema\/fda-common-issues-requested-discussion-respective-agency-ema\/pdco-fda-concerning-paediatric-oncology-devlopment-plans-paediatric-investigation-plans-pips_en.pdf\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib137","article-title":"Common commentary on paediatric oncology drug development. ther innov regul","author":"Karres","year":"2021","journal-title":"Sci"},{"key":"10.1016\/j.ejca.2024.114145_bib138","unstructured":"Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients. https:\/\/clinicaltrials.gov\/study\/NCT03458728. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib139","unstructured":"IPI-145 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL) \u3008https:\/\/clinicaltrials.gov\/study\/NCT02028039\u3009. (Accessed 19 November 2023)."},{"key":"10.1016\/j.ejca.2024.114145_bib151","unstructured":"Study of Miransertib (MK-7075) in Participants With PIK3CA-related Overgrowth Spectrum and Proteus Syndrome (MOSAIC) (MK-7075\u2013002) (MOSAIC). \u3008https:\/\/clinicaltrials.gov\/study\/NCT03094832\u3009. (Accessed 19 November 2023)."}],"container-title":["European Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959804924008013?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959804924008013?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:22:03Z","timestamp":1786969323000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959804924008013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":129,"alternative-id":["S0959804924008013"],"URL":"https:\/\/doi.org\/10.1016\/j.ejca.2024.114145","relation":{},"ISSN":["0959-8049"],"issn-type":[{"value":"0959-8049","type":"print"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Paediatric strategy forum for medicinal product development of PI3-K, mTOR, AKT and GSK3\u03b2 inhibitors in children and adolescents with cancer","name":"articletitle","label":"Article Title"},{"value":"European Journal of Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejca.2024.114145","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"114145"}}