ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine.The journal of headache and pain · 2026Article
- Shuangdong Capsule Activates Insulin Signal Pathway to Improve Urinary Tract Infection in Diabetic Rats.Combinatorial chemistry & high throughput screening · 2025Article
- Familial CCM Genes Might Not Be Main Drivers for Pathogenesis of Sporadic CCMs-Genetic Similarity between Cancers and Vascular Malformations.Journal of personalized medicine · 2023Review
- Safety of Sirolimus in Patients with Tuberous Sclerosis Complex under Two Years of Age-A Bicenter Retrospective Study.Journal of clinical medicine · 2023Article
- FK506 increases susceptibility to musculoskeletal infection in a rodent model.BMC musculoskeletal disorders · 2022Article
- 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
- Endothelial mTOR maintains hematopoiesis during aging.The Journal of experimental medicine · 2020Article
- Article
- Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells.Scientific reports · 2019Article
- Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Article
- Global Proteomics RevealedFrontiers in cellular and infection microbiology · 2017Article
- Insulin and the phosphatidylinositol 3-kinase signaling pathway regulate Ribonuclease 7 expression in the human urinary tract.Kidney international · 2016Article
- Hyperglycemia and Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) Inhibitors in Phase I Trials: Incidence, Predictive Factors, and Management.The oncologist · 2016Article
- Molecular Pathways: Increased Susceptibility to Infection Is a Complication of mTOR Inhibitor Use in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- Immunomodulation and Disease Tolerance to Staphylococcus aureus.Pathogens (Basel, Switzerland) · 2015Review
- Risk of Infectious Complications in Hemato-Oncological Patients Treated with Kinase Inhibitors.Biomarker insights · 2015Review
- Risk of infection associated with targeted therapies for solid organ and hematological malignancies.Therapeutic advances in infectious diseaseReview
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
purposeNovel antitumor therapies against the PI3K-AKT-mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. Although these agents are not known to be myelosuppressive, an increased risk of infection has been reported with rapamycin analogues. However, the risk of infection with new inhibitors of this pathway such as PI3K, AKT, mTORC 1/2, or multikinase inhibitors is unknown. EXPERIMENTAL
designIn this retrospective case-control study, we determined the incidence of infection in a group of 432 patients who were treated on 15 phase I clinical trials involving PI3K-AKT-mTOR pathway inhibitors (cases) versus a group of 100 patients on 10 phase I clinical trials of single agent non-PI3K-AKT-mTOR pathway inhibitors (controls) which did not involve conventional cytotoxic agents. We also collected data from 42 patients who were treated with phase I trials of combinations of PI3K-AKT-mTOR inhibitors and MEK inhibitors and 24 patients with combinations of PI3K-AKT-mTOR inhibitors and cytotoxic chemotherapies.
resultsThe incidence of all grade infection was significantly higher with all single-agent PI3K-AKT-mTOR inhibitors compared with the control group [27% vs. 8%, respectively, OR, 4.26; 95% confidence intervals (CI), 1.9-9.1, P = 0.0001]. The incidence of grade 3 and 4 infection was also significantly higher with PI3K-AKT-mTOR inhibitors compared with the control group (10.3% vs. 3%, OR, 3.74; 95% CI, 1.1-12.4; P = 0.02). Also, the combination of PI3K-AKT-mTOR inhibitors and chemotherapy was associated with a significantly higher incidence of all grade (OR, 4.79; 95% CI, 2.0-11.2; P = 0.0001) and high-grade (OR, 2.87; 95% CI, 1.0-7.6; P = 0.03) infection when compared with single-agent PI3K-AKT-mTOR inhibitors.
conclusionsInhibitors of the PI3K-AKT-mTOR pathway can be associated with a higher risk of infection. Combinations of PI3K-AKT-mTOR inhibitors and cytotoxic chemotherapy significantly increase the risk of infection. This should be taken into consideration during the design and conduct of trials involving PI3K-AKT-mTOR pathway inhibitors, particularly when combined with chemotherapy or myelosuppressive agents.
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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.