{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:12:35Z","timestamp":1771272755139,"version":"3.50.1"},"reference-count":99,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11]]},"DOI":"10.1097\/cco.0b013e328358a2b5","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T07:36:22Z","timestamp":1347003382000},"page":"623-634","source":"Crossref","is-referenced-by-count":43,"title":["Phosphatidylinositol 3-kinase\/AKT\/mammalian target of rapamycin pathway inhibition"],"prefix":"10.1097","volume":"24","author":[{"given":"Dimitrios","family":"Zardavas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Fumagalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherene","family":"Loi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-5-20210128","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1038\/onc.2008.244","article-title":"Class I PI3K in oncogenic cellular transformation.","volume":"27","author":"Zhao","year":"2008","journal-title":"Oncogene"},{"key":"R2-5-20210128","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/0092-8674(93)90404-E","article-title":"SH2 domains recognize specific phosphopeptide sequences.","volume":"72","author":"Songyang","year":"1993","journal-title":"Cell"},{"key":"R3-5-20210128","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nrg1879","article-title":"The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.","volume":"7","author":"Engelman","year":"2006","journal-title":"Nat Rev Genet"},{"key":"R4-5-20210128","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1126\/science.279.5351.710","article-title":"Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B.","volume":"279","author":"Stephens","year":"1998","journal-title":"Science"},{"key":"R5-5-20210128","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKTPKB signaling: navigating downstream.","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"R6-5-20210128","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism.","volume":"124","author":"Wullschleger","year":"2006","journal-title":"Cell"},{"key":"R7-5-20210128","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0092-8674(02)00808-5","article-title":"mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.","volume":"110","author":"Kim","year":"2002","journal-title":"Cell"},{"key":"R8-5-20210128","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","article-title":"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.","volume":"14","author":"Sarbassov","year":"2004","journal-title":"Curr Biol"},{"key":"R9-5-20210128","first-page":"97","article-title":"PTEN and p53: who will get the upper hand Cancer C","volume":"3","author":"Trotman","year":"2003","journal-title":"ell"},{"key":"R10-5-20210128","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","article-title":"The phosphoinositide 3-kinase pathway.","volume":"296","author":"Cantley","year":"2002","journal-title":"Science"},{"key":"R11-5-20210128","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ccr.2009.06.006","article-title":"Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling.","volume":"16","author":"Gewinner","year":"2009","journal-title":"Cancer Cell"},{"key":"R12-5-20210128","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/S0140-6736(05)66544-0","article-title":"Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.","volume":"365","year":"2005","journal-title":"Lancet"},{"key":"R13-5-20210128","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev-med-070909-182917","article-title":"Mechanisms of endocrine resistance in breast cancer.","volume":"62","author":"Osborne","year":"2011","journal-title":"Annu Rev Med"},{"key":"R14-5-20210128","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nrc2713","article-title":"Biological determinants of endocrine resistance in breast cancer.","volume":"9","author":"Musgrove","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"R15-5-20210128","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1158\/1078-0432.CCR-07-1046","article-title":"Down-regulation of phosphatidylinositol 3-kinaseAKTmolecular target of rapamycin metabolic pathway by primary letrozole-based therapy in human breast cancer.","volume":"14","author":"Generali","year":"2008","journal-title":"Clin Cancer Res"},{"key":"R16-5-20210128","first-page":"5985","article-title":"Phosphatidylinositol-3-OH kinase (PI3K)AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K.","volume":"61","author":"Sun","year":"2001","journal-title":"Cancer Res"},{"key":"R17-5-20210128","doi-asserted-by":"crossref","first-page":"331S","DOI":"10.1158\/1078-0432.CCR-031212","article-title":"Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance.","volume":"10","author":"Schiff","year":"2004","journal-title":"Clin Cancer Res"},{"key":"R18-5-20210128","doi-asserted-by":"crossref","first-page":"9817","DOI":"10.1074\/jbc.M010840200","article-title":"Phosphatidylinositol 3-kinaseAKT-mediated activation of estrogen receptor alpha: a new model for antiestrogen resistance.","volume":"276","author":"Campbell","year":"2001","journal-title":"J Biol Chem"},{"key":"R19-5-20210128","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1200\/JCO.2005.10.036","article-title":"Estrogen-receptor biology: continuing progress and therapeutic implications.","volume":"23","author":"Osborne","year":"2005","journal-title":"J Clin Oncol"},{"key":"R20-5-20210128","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1074\/jbc.M807532200","article-title":"S6 kinase 1 regulates estrogen receptor alpha in control of breast cancer cell proliferation.","volume":"284","author":"Yamnik","year":"2009","journal-title":"J Biol Chem"},{"key":"R21-5-20210128","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1200\/JCO.2010.34.4879","article-title":"Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer.","volume":"29","author":"Miller","year":"2011","journal-title":"J Clin Oncol"},{"key":"R22-5-20210128","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1158\/0008-5472.CAN-07-2707","article-title":"Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function.","volume":"68","author":"Massarweh","year":"2008","journal-title":"Cancer Res"},{"key":"R23-5-20210128","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ghir.2006.06.005","article-title":"Insulin-like growth factor binding protein 2 is a marker for antiestrogen resistant human breast cancer cell lines but is not a major growth regulator.","volume":"16","author":"Juncker-Jensen","year":"2006","journal-title":"Growth Horm IGF Res"},{"key":"R24-5-20210128","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1172\/JCI41680","article-title":"Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer.","volume":"120","author":"Miller","year":"2010","journal-title":"J Clin Invest"},{"key":"R25-5-20210128","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1093\/annonc\/mdm170","article-title":"Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling.","volume":"18","author":"Beeram","year":"2007","journal-title":"Ann Oncol"},{"key":"R26-5-20210128","doi-asserted-by":"crossref","first-page":"8059","DOI":"10.1158\/1078-0432.CCR-04-0035","article-title":"Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity.","volume":"10","author":"deGraffenried LA, Friedrichs","year":"2004","journal-title":"Clin Cancer Res"},{"key":"R27-5-20210128","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1158\/0008-5472.CAN-09-0042","article-title":"Loss of phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer.","volume":"69","author":"Miller","year":"2009","journal-title":"Cancer Res"},{"key":"R29-5-20210128","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.1158\/1078-0432.CCR-09-0632","article-title":"PIK3CA mutation associates with improved outcome in breast cancer.","volume":"15","author":"Kalinsky","year":"2009","journal-title":"Clin Cancer Res"},{"key":"R30-5-20210128","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1158\/0008-5472.CAN-07-6854","article-title":"An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer.","volume":"68","author":"Stemke-Hale","year":"2008","journal-title":"Cancer Res"},{"key":"R31-5-20210128","doi-asserted-by":"crossref","first-page":"R28","DOI":"10.1186\/bcr3113","article-title":"PIK3CA mutation impact on survival in breast cancer patients and in ER, PR and ERBB2-based subgroups.","volume":"14","author":"Cizkova","year":"2012","journal-title":"Breast Cancer Res: BCR"},{"key":"R32-5-20210128","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1038\/onc.2008.170","article-title":"AKT1(E17K) in human solid tumours.","volume":"27","author":"Bleeker","year":"2008","journal-title":"Oncogene"},{"key":"R33-5-20210128","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1158\/1078-0432.CCR-06-1609","article-title":"PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer.","volume":"13","author":"Perez-Tenorio","year":"2007","journal-title":"Clin Cancer Res"},{"key":"R34-5-20210128","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10549-005-9048-0","article-title":"PIK3CA mutations in breast cancer are associated with poor outcome.","volume":"96","author":"Li","year":"2005","journal-title":"Breast Cancer Res Treat"},{"key":"R35-5-20210128","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/path.1908","article-title":"PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma.","volume":"208","author":"Buttitta","year":"2006","journal-title":"J Pathol"},{"key":"R36-5-20210128","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1158\/1078-0432.CCR-06-0267","article-title":"Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women.","volume":"13","author":"Maruyama","year":"2007","journal-title":"Clin Cancer Res"},{"key":"R37-5-20210128","doi-asserted-by":"crossref","first-page":"10208","DOI":"10.1073\/pnas.0907011107","article-title":"PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer.","volume":"107","author":"Loi","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R38-5-20210128","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":"R39-5-20210128","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1245\/s10434-007-9751-7","article-title":"PIK3CA exon 20 mutation is independently associated with a poor prognosis in breast cancer patients.","volume":"15","author":"Lai","year":"2008","journal-title":"Ann Surg Oncol"},{"key":"R40-5-20210128","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10549-006-9295-8","article-title":"Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma.","volume":"101","author":"Tokunaga","year":"2006","journal-title":"Breast Cancer Res Treat"},{"key":"R41-5-20210128","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.yexmp.2009.09.016","article-title":"PIK3CA mutations mostly begin to develop in ductal carcinoma of the breast.","volume":"88","author":"Li","year":"2010","journal-title":"Exp Mol Pathol"},{"key":"R42-5-20210128","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/ijc.2910640412","article-title":"Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas.","volume":"64","author":"Bellacosa","year":"1995","journal-title":"Int J Cancer"},{"key":"R43-5-20210128","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1023\/A:1006273516976","article-title":"Allelic loss of the PTEN region (10q23) in breast carcinomas of poor pathophenotype.","volume":"57","author":"Garcia","year":"1999","journal-title":"Breast Cancer Res Treat"},{"key":"R44-5-20210128","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1365-2559.2009.03467.x","article-title":"Molecular alterations in AKT1, AKT2 and AKT3 detected in breast and prostatic cancer by FISH.","volume":"56","author":"Kirkegaard","year":"2010","journal-title":"Histopathology"},{"key":"R45-5-20210128","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/sj.bjc.6690121","article-title":"Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas.","volume":"79","author":"Freihoff","year":"1999","journal-title":"Br J Cancer"},{"key":"R46-5-20210128","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1038\/sj.bjc.6604212","article-title":"Mutational analysis of oncogenic AKT E17K mutation in common solid cancers and acute leukaemias.","volume":"98","author":"Kim","year":"2008","journal-title":"Br J Cancer"},{"key":"R47-5-20210128","doi-asserted-by":"crossref","first-page":"R609","DOI":"10.1186\/bcr1262","article-title":"Somatic mutation and gain of copy number of PIK3CA in human breast cancer.","volume":"7","author":"Wu","year":"2005","journal-title":"Breast Cancer Res"},{"key":"R48-5-20210128","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1158\/1078-0432.CCR-04-2142","article-title":"Frequent mutation of the PIK3CA gene in ovarian and breast cancers.","volume":"11","author":"Levine","year":"2005","journal-title":"Clin Cancer Res"},{"key":"R49-5-20210128","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/sj.bjc.6690115","article-title":"Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma.","volume":"79","author":"Feilotter","year":"1999","journal-title":"Br J Cancer"},{"key":"R50-5-20210128","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nature05933","article-title":"A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.","volume":"448","author":"Carpten","year":"2007","journal-title":"Nature"},{"key":"R51-5-20210128","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ccr.2007.08.030","article-title":"A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer.","volume":"12","author":"Berns","year":"2007","journal-title":"Cancer Cell"},{"key":"R52-5-20210128","doi-asserted-by":"crossref","first-page":"772","DOI":"10.4161\/cbt.3.8.994","article-title":"The PIK3CA gene is mutated with high frequency in human breast cancers.","volume":"3","author":"Bachman","year":"2004","journal-title":"Cancer Biol Ther"},{"key":"R53-5-20210128","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/ng.2007.39","article-title":"Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair.","volume":"40","author":"Saal","year":"2007","journal-title":"Nat Genet"},{"key":"R54-5-20210128","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cancergencyto.2008.07.005","article-title":"PIK3CA gene mutations in breast carcinoma in Malaysian patients.","volume":"187","author":"Ching-Shian Leong","year":"2008","journal-title":"Cancer Genet Cytogenet"},{"key":"R55-5-20210128","doi-asserted-by":"crossref","first-page":"18443","DOI":"10.1073\/pnas.0508988102","article-title":"The oncogenic properties of mutant p110 and p110 phosphatidylinositol 3-kinases in human mammary epithelial cells.","volume":"102","author":"Zhao","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R56-5-20210128","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":"R57-5-20210128","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.1096502","article-title":"High frequency of mutations of the PIK3CA gene in human cancers.","volume":"304","author":"Samuels","year":"2004","journal-title":"Science"},{"key":"R58-5-20210128","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":"R59-5-20210128","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":"R60-5-20210128","first-page":"3147","article-title":"Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay.","volume":"60","author":"Han","year":"2000","journal-title":"Cancer Res"},{"key":"R61-5-20210128","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/gcc.20062","article-title":"Promoter methylation of the PTEN gene is a common molecular change in breast cancer.","volume":"41","author":"Garcia","year":"2004","journal-title":"Genes Chromosomes Cancer"},{"key":"R62-5-20210128","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ccr.2007.07.014","article-title":"A new mutational AKTivation in the PI3K pathway.","volume":"12","author":"Brugge","year":"2007","journal-title":"Cancer Cell"},{"key":"R63-5-20210128","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10549-009-0575-y","article-title":"Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer.","volume":"119","author":"Ellis","year":"2009","journal-title":"Breast Cancer Res Treat"},{"key":"R64-5-20210128","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1210\/er.2006-0045","article-title":"Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: molecular mechanism and clinical implications for endocrine therapy resistance.","volume":"29","author":"Arpino","year":"2008","journal-title":"Endocr Rev"},{"key":"R65-5-20210128","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.bbrc.2005.12.025","article-title":"Correlation of PIK3Ca mutations with gene expression and drug sensitivity in NCI-60 cell lines.","volume":"340","author":"Whyte","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"R66-5-20210128","doi-asserted-by":"crossref","first-page":"e3065","DOI":"10.1371\/journal.pone.0003065","article-title":"Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling.","volume":"3","author":"She","year":"2008","journal-title":"PLoS ONE"},{"key":"R67-5-20210128","doi-asserted-by":"crossref","first-page":"7564","DOI":"10.1073\/pnas.0702507104","article-title":"Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity.","volume":"104","author":"Saal","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R68-5-20210128","doi-asserted-by":"crossref","first-page":"R40","DOI":"10.1186\/bcr2594","article-title":"Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER breast cancer.","volume":"12","author":"Creighton","year":"2010","journal-title":"Breast Cancer Res"},{"key":"R69-5-20210128","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/bcr2904","article-title":"Luminal-B breast cancer and novel therapeutic targets.","volume":"13","author":"Tran","year":"2011","journal-title":"Breast Cancer Res"},{"key":"R70-5-20210128","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature10912","article-title":"The translational landscape of mTOR signalling steers cancer initiation and metastasis.","volume":"485","author":"Hsieh","year":"2012","journal-title":"Nature"},{"key":"R71-5-20210128","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nrclinonc.2010.21","article-title":"mTOR signaling and drug development in cancer.","volume":"7","author":"Dancey","year":"2010","journal-title":"Nat Rev Clin Oncol"},{"key":"R72-5-20210128","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1200\/JCO.2008.20.0766","article-title":"Targeting the mTOR signaling network for cancer therapy.","volume":"27","author":"Meric-Bernstam","year":"2009","journal-title":"J Clin Oncol"},{"key":"R73-5-20210128","doi-asserted-by":"crossref","first-page":"5314","DOI":"10.1200\/JCO.2005.66.130","article-title":"Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer.","volume":"23","author":"Chan","year":"2005","journal-title":"J Clin Oncol"},{"key":"R74-5-20210128","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1200\/jco.2005.23.16_suppl.564","article-title":"Randomized 3-arm, phase 2 study of temsirolimus (CCI-779) in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer. Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.","volume":"23","author":"Carpenter","year":"2005","journal-title":"J Clin Oncol"},{"issue":"suppl 1","key":"R75-5-20210128","first-page":"6091","article-title":"Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer abstract.","volume":"100","author":"Chow","year":"2006","journal-title":"Breast Cancer Res Treat"},{"key":"R76-5-20210128","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejca.2007.10.003","article-title":"The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics.","volume":"44","author":"Awada","year":"2008","journal-title":"Eur J Cancer"},{"key":"R77-5-20210128","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1200\/JCO.2008.18.8391","article-title":"Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer.","volume":"27","author":"Baselga","year":"2009","journal-title":"J Clin Oncol"},{"key":"R79-5-20210128","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJMoa1109653","article-title":"Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.","volume":"366","author":"Baselga","year":"2012","journal-title":"N Engl J Med"},{"key":"R80-5-20210128","doi-asserted-by":"crossref","first-page":"5319","DOI":"10.1158\/1078-0432.CCR-04-2402","article-title":"Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer.","volume":"11","author":"Boulay","year":"2005","journal-title":"Clin Cancer Res"},{"key":"R81-5-20210128","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1158\/0008-5472.CAN-08-4450","article-title":"PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer.","volume":"69","author":"Crowder","year":"2009","journal-title":"Cancer Res"},{"key":"R82-5-20210128","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4161\/cc.8.4.7659","article-title":"Not all substrates are treated equally: implications for mTOR, rapamycin-resistance and cancer therapy.","volume":"8","author":"Choo","year":"2009","journal-title":"Cell Cycle"},{"key":"R83-5-20210128","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1083\/jcb.200403069","article-title":"The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins.","volume":"166","author":"Harrington","year":"2004","journal-title":"J Cell Biol"},{"key":"R84-5-20210128","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1128\/MCB.00601-09","article-title":"mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling.","volume":"30","author":"Julien","year":"2010","journal-title":"Mol Cell Biol"},{"key":"R85-5-20210128","doi-asserted-by":"crossref","first-page":"22299","DOI":"10.1073\/pnas.0905152106","article-title":"Specific apoptosis induction by the dual PI3KmTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells.","volume":"106","author":"Brachmann","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R86-5-20210128","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1158\/1535-7163.MCT-09-0160","article-title":"NVP-BEZ235, a novel dual phosphatidylinositol 3-kinasemammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas.","volume":"8","author":"Liu","year":"2009","journal-title":"Mol Cancer Ther"},{"key":"R87-5-20210128","doi-asserted-by":"crossref","first-page":"13057","DOI":"10.1073\/pnas.0802655105","article-title":"PTEN-deficient cancers depend on PIK3CB.","volume":"105","author":"Wee","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R88-5-20210128","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/2159-8290.CD-12-0003","article-title":"Functional characterization of an isoform-selective inhibitor of PI3K-p110 as a potential anticancer agent.","volume":"2","author":"Ni","year":"2012","journal-title":"Cancer Discov"},{"key":"R89-5-20210128","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1517\/13543776.2011.587959","article-title":"Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape.","volume":"21","author":"Mattmann","year":"2011","journal-title":"Expert Opin Ther Pat"},{"key":"R92-5-20210128","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1158\/1078-0432.CCR-09-2828","article-title":"Predictive biomarkers of sensitivity to the phosphatidylinositol 3 kinase inhibitor GDC-0941 in breast cancer preclinical models.","volume":"16","author":"OBrien","year":"2010","journal-title":"Clin Cancer Res"},{"key":"R93-5-20210128","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1200\/JCO.2011.36.1196","article-title":"PI3KAKTmTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations.","volume":"30","author":"Janku","year":"2012","journal-title":"J Clin Oncol"},{"key":"R94-5-20210128","first-page":"3065","article-title":"Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer.","volume":"118","author":"Carracedo","year":"2008","journal-title":"J Clin Invest"},{"key":"R95-5-20210128","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1158\/0008-5472.CAN-07-6656","article-title":"Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance.","volume":"69","author":"Ihle","year":"2009","journal-title":"Cancer Res"},{"key":"R96-5-20210128","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1200\/JCO.2011.36.1360","article-title":"Phase I, dose-escalation study of BKM120, an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors.","volume":"30","author":"Bendell","year":"2012","journal-title":"J Clin Oncol"},{"key":"R98-5-20210128","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/bcr2906","article-title":"Minimal residual disease and circulating tumor cells in breast cancer.","volume":"13","author":"Ignatiadis","year":"2011","journal-title":"Breast Cancer Res"},{"key":"R100-5-20210128","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s10549-010-0747-9","article-title":"Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer.","volume":"120","author":"Board","year":"2010","journal-title":"Breast Cancer Res Treat"},{"key":"R101-5-20210128","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.cell.2012.04.024","article-title":"Mutational processes molding the genomes of 21 breast cancers.","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"R102-5-20210128","doi-asserted-by":"crossref","first-page":"127s10","DOI":"10.1126\/scitranslmed.3003854","article-title":"Intratumor heterogeneity: seeing the wood for the trees.","volume":"4","author":"Yap","year":"2012","journal-title":"Sci Transl Med"},{"key":"R103-5-20210128","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1158\/1535-7163.MCT-10-1089","article-title":"PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer.","volume":"10","author":"Gonzalez-Angulo","year":"2011","journal-title":"Mol Cancer Therap"},{"key":"R104-5-20210128","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1158\/1078-0432.CCR-10-1133","article-title":"PIK3CA Mutations may be discordant between primary and corresponding metastatic disease in breast cancer.","volume":"17","author":"Dupont Jensen","year":"2010","journal-title":"Clin Cancer Res"},{"key":"R105-5-20210128","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1158\/0008-5472.CAN-08-2660","article-title":"PIK3CA mutations in in situ and invasive breast carcinomas.","volume":"70","author":"Miron","year":"2010","journal-title":"Cancer Res"}],"container-title":["Current Opinion in Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/CCO.0b013e328358a2b5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T19:38:29Z","timestamp":1621885109000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00001622-201211000-00005"}},"subtitle":["a breakthrough in the management of luminal (ER+\/HER2\u2212) breast cancers?"],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":99,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.1097\/cco.0b013e328358a2b5","relation":{},"ISSN":["1040-8746"],"issn-type":[{"value":"1040-8746","type":"print"}],"subject":[],"published":{"date-parts":[[2012,11]]}}}