ReviewOncotarget2012
Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment.
Review in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
74 citing papers in PubMed, 122 citations in OpenAlex.
- Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial.Head & neck · 2015Trial
- Targeting autophagy in dysfunctional tumor vasculature.iScience · 2025Review
- The apoptotic and anti-proliferative effects of Neosetophomone B in T-cell acute lymphoblastic leukaemia via PI3K/AKT/mTOR pathway inhibition.Cell proliferation · 2025Article
- Pathway of LCK Tyrosine Kinase and mTOR Signaling in Children with T-Cell Acute Lymphoblastic Leukemia.The application of clinical genetics · 2024Review
- Article
- Review
- Mechanism and Role of Endoplasmic Reticulum Stress in Osteosarcoma.Biomolecules · 2022Review
- PI3K/mTOR inhibition prevents anal cancer in mice with established low-grade anal dysplasia.Experimental and molecular pathology · 2022Article
- Identification of Prognostic Biomarkers in Patients With Malignant Rhabdoid Tumor of the Kidney Based on mTORC1 Signaling Pathway-Related Genes.Frontiers in molecular biosciences · 2022Article
- Dual targeting of MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia.Leukemia · 2021Article
- New Therapeutic Opportunities for the Treatment of Squamous Cell Carcinomas: A Focus on Novel Driver Kinases.International journal of molecular sciences · 2021Review
- Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021Article
- T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies.Blood cancer discovery · 2021Review
- B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?Cancers · 2020Review
- Novel nanococktail of a dual PI3K/mTOR inhibitor and cabazitaxel for castration-resistant prostate cancer.Advanced therapeutics · 2020Article
- A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia.BMC pharmacology & toxicology · 2020Article
- Fasting to enhance Cancer treatment in models: the next steps.Journal of biomedical science · 2020Review
- Is There a Role for Dual PI3K/mTOR Inhibitors for Patients Affected with Lymphoma?International journal of molecular sciences · 2020Review
- Targeting mTOR in Acute Lymphoblastic Leukemia.Cells · 2019Review
- Oncogenic kinases and perturbations in protein synthesis machinery and energetics in neoplasia.Journal of molecular endocrinology · 2019Review
14 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
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) are two key components of the PI3K/Akt/mTOR signaling pathway. This signal transduction cascade regulates a wide range of physiological cell processes, that include differentiation, proliferation, apoptosis, autophagy, metabolism, motility, and exocytosis. However, constitutively active PI3K/Akt/mTOR signaling characterizes many types of tumors where it negatively influences response to therapeutic treatments. Hence, targeting PI3K/Akt/mTOR signaling with small molecule inhibitors may improve cancer patient outcome. The PI3K/Akt/mTOR signaling cascade is overactive in acute leukemias, where it correlates with enhanced drug-resistance and poor prognosis. The catalytic sites of PI3K and mTOR share a high degree of sequence homology. This feature has allowed the synthesis of ATP-competitive compounds targeting the catalytic site of both kinases. In preclinical models, dual PI3K/mTOR inhibitors displayed a much stronger cytotoxicity against acute leukemia cells than either PI3K inhibitors or allosteric mTOR inhibitors, such as rapamycin. At variance with rapamycin, dual PI3K/mTOR inhibitors targeted both mTOR complex 1 and mTOR complex 2, and inhibited the rapamycin-resistant phosphorylation of eukaryotic initiation factor 4E-binding protein 1, resulting in a marked inhibition of oncogenic protein translation. Therefore, they strongly reduced cell proliferation and induced an important apoptotic response. Here, we reviewed the evidence documenting that dual PI3K/mTOR inhibitors may represent a promising option for future targeted therapies of acute leukemia patients.
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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 Socratic graph.