ArticleBritish journal of cancer2015
Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Treatment-related adverse events in patients with advanced breast cancer receiving adjuvant AKT inhibitors: a meta-analysis of randomized controlled trials.European journal of clinical pharmacology · 2024Pooled it
- Targeting the PI3K/AKT/mTOR pathway in gastrointestinal cancers: a comprehensive review of mechanisms, preclinical evidence, and clinical challenges.Medical oncology (Northwood, London, England) · 2026Review
- FOXO transcription factors in Alzheimer's Disease: balancing neuroprotection and neuronal degeneration.Molecular biology reports · 2026Review
- p70S6K/Akt dual inhibitor DIACC3010 is efficacious in preclinical models of gastric cancer alone and in combination with trastuzumab.Scientific reports · 2023Article
- Risk Factors of Hyperglycemia After Treatment With the AKT Inhibitor Ipatasertib in the Prostate Cancer Setting: A Machine Learning-Based Investigation.JCO clinical cancer informatics · 2023Article
- Mechanically activated ion channel Piezo1 contributes to melanoma malignant progression through AKT/mTOR signaling.Cancer biology & therapy · 2022Article
- Severe Lactic Acidosis Complicated by Insulin-Resistant Hyperosmolar Hyperglycemic Syndrome in a Patient With Metastatic Breast Cancer Undergoing AKT-Inhibitor Therapy.JCO precision oncology · 2022Article
- Insulin and cancer: a tangled web.The Biochemical journal · 2022Review
- Screening of a Panel of Low Molecular Weight Compounds That Inhibit Synovial Fibroblast Invasion in Rheumatoid Arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Prolonged treatment with a PI3K p110α inhibitor causes sex- and tissue-dependent changes in antioxidant content, but does not affect mitochondrial function.Bioscience reports · 2020Article
- First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Cancer Biology and Prevention in Diabetes.Cells · 2020Review
- Exploiting the folate receptor α in oncology.Nature reviews. Clinical oncology · 2020Review
- Melatonin Prevents Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis in High Glucose-Treated Schwann Cells via Upregulation of Bcl2, NF-κB, mTOR, Wnt Signalling Pathways.Antioxidants (Basel, Switzerland) · 2019Article
- Dietary Carbohydrate Promotes Cell Survival in Cancer Via the Up-Regulation of Fat Mass and Obesity-Associated Gene Expression Level.The Malaysian journal of medical sciences : MJMS · 2019Review
- The Akt pathway in oncology therapy and beyond (Review).International journal of oncology · 2018Review
- Nanoparticles That Reshape the Tumor Milieu Create a Therapeutic Window for Effective T-cell Therapy in Solid Malignancies.Cancer research · 2018Article
- Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?Nature reviews. Clinical oncology · 2017Review
- Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Review
- From obesity to diabetes and cancer: epidemiological links and role of therapies.British journal of cancer · 2016Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients.
methodsRetrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups.
resultsThe incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3-4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3-4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients.
conclusionsPI3K-AKT-mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers.
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Registered trials
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