ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
PIK3CA/PTEN mutations and Akt activation as markers of sensitivity to allosteric mTOR inhibitors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- Comparison of mTOR inhibitors combined with endocrine therapy versus that alone in breast cancer: a meta-analysis.Future oncology (London, England) · 2025Pooled it
- Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer.Breast cancer research : BCR · 2020Trial
- A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index.Cancer prevention research (Philadelphia, Pa.) · 2020Trial
- Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors.The oncologist · 2018Trial
- Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study.Lancet (London, England) · 2016Trial
- A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K.Neuro-oncology · 2015Trial
- Trial
- Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer†.Annals of oncology : official journal of the European Society for Medical Oncology · 2014Trial
- The Genomic Patterns of Well-Differentiated Pancreatic Neuroendocrine Tumors (NETs) Identify Sub-Sets for Rational Therapeutic Targeting.International journal of molecular sciences · 2026Article
- Systemic Everolimus Does Not Block the Incubation of Methamphetamine-Craving: A Dose-Response Study.Addiction biology · 2026Article
- Genetics and Molecular Mechanisms in Oral Squamous Cell Carcinoma: A Narrative Review.Medicina (Kaunas, Lithuania) · 2026Review
- Impact of High-Risk HPV Infection on PI3K, MALAT1, H19 and LINC00460 Expression in Cervical Cells.Journal of cellular and molecular medicine · 2025Article
- METTL3 stabilizes DDX17 mRNA via IGF2BP2-mediated m6A modification to suppress endometrial cancer progression.Clinical and experimental medicine · 2025Article
- Repurposing Amiodarone for Bladder Cancer Treatment.Cancer research communications · 2025Article
- Real-world evidence couples genomic biomarkers with therapeutic outcomes for canine hemangiosarcoma.Scientific reports · 2025Article
- Characteristics and impact of real-world evidence studies in oncology: comprehensive mapping review of publications evaluating targeted therapies in solid tumours.ESMO real world data and digital oncology · 2024Review
- Identification of novel inhibitors targeting PI3Kα via ensemble-based virtual screening method, biological evaluation and molecular dynamics simulation.Journal of computer-aided molecular design · 2024Article
- HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.International journal of biological sciences · 2024Article
- mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation.Frontiers in oncology · 2024Review
- Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma.International journal of molecular sciences · 2023Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe sought to determine whether phosphoinositide 3-kinase (PI3K) pathway mutation or activation state and rapamycin-induced feedback loop activation of Akt is associated with rapamycin sensitivity or resistance. EXPERIMENTAL
designCancer cell lines were tested for rapamycin sensitivity, Akt phosphorylation, and mTOR target inhibition. Mice injected with breast or neuroendocrine cancer cells and patients with neuroendocrine tumor (NET) were treated with rapalogs and Akt phosphorylation was assessed.
resultsThirty-one cell lines were rapamycin sensitive (RS) and 12 were relatively rapamycin resistant (RR; IC(50) > 100 nmol/L). Cells with PIK3CA and/or PTEN mutations were more likely to be RS (P = 0.0123). Akt phosphorylation (S473 and T308) was significantly higher in RS cells (P < 0.0001). Rapamycin led to a significantly greater pathway inhibition and greater increase in p-Akt T308 (P < 0.0001) and p-Akt S473 (P = 0.0009) in RS cells. Rapamycin and everolimus significantly increased Akt phosphorylation but inhibited growth in an in vivo NET model (BON). In patients with NETs treated with everolimus and octreotide, progression-free survival correlated with p-Akt T308 in pretreatment (R = 0.4762, P = 0.0533) and on-treatment tumor biopsies (R = 0.6041, P = 0.0102). Patients who had a documented partial response were more likely to have an increase in p-Akt T308 with treatment compared with nonresponders (P = 0.0146).
conclusionPIK3CA/PTEN genomic aberrations and high p-Akt levels are associated with rapamycin sensitivity in vitro. Rapamycin-mediated Akt activation is greater in RS cells, with a similar observation in patients with clinical responses on exploratory biomarker analysis; thus feedback loop activation of Akt is not a marker of resistance but rather may function as an indicator of rapamycin activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.