ReviewFrontiers in physiology2014
Allosteric modulation of Ras and the PI3K/AKT/mTOR pathway: emerging therapeutic opportunities.
Review in Frontiers in physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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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.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- EGFR Mutations and Tyrosine Kinase Inhibitors: Structural Insights and Therapeutic Advances.ACS omega · 2026Review
- Statins regulate kinase signaling by causing changes in phosphorylation, rather than through changes in gene expression or direct inhibition: evidence in colorectal cancer.Frontiers in pharmacology · 2025Article
- Krüppel-like factor 12 decreases progestin sensitivity in endometrial cancer by inhibiting the progesterone receptor signaling pathway.Translational oncology · 2024Article
- In Silico Exploration of Novel EGFR Kinase Mutant-Selective Inhibitors Using a Hybrid Computational Approach.Pharmaceuticals (Basel, Switzerland) · 2024Article
- PARP inhibitors in the treatment of ARID1A mutant ovarian clear cell cancer: PI3K/Akt1-dependent mechanism of synthetic lethality.Frontiers in oncology · 2023Article
- Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects.International journal of molecular sciences · 2022Review
- Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- MiR-873-5p: A Potential Molecular Marker for Cancer Diagnosis and Prognosis.Frontiers in oncology · 2021Review
- Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance.Pharmacological reports : PR · 2020Review
- AMPH1 functions as a tumour suppressor in ovarian cancer via the inactivation of PI3K/AKT pathway.Journal of cellular and molecular medicine · 2020Article
- Article
- Decreased expression of TRPM4 is associated with unfavorable prognosis and aggressive progression of endometrial carcinoma.American journal of translational research · 2020Article
- Sinomenine sensitizes human gastric cancer cells to cisplatin through negative regulation of PI3K/AKT/Wnt signaling pathway.Anti-cancer drugs · 2019Article
- Diabetic Pregnancy and Maternal High-Fat Diet Impair Mitochondrial Dynamism in the Developing Fetal Rat Heart by Sex-Specific Mechanisms.International journal of molecular sciences · 2019Article
- The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers.Molecular therapy. Nucleic acids · 2019Article
- Does Ras Activate Raf and PI3K Allosterically?Frontiers in oncology · 2019Review
- PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target.Virulence · 2018Article
- Genome-scale analysis to identify prognostic markers in patients with early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy.OncoTargets and therapy · 2017Article
- PI3K/AKT/mTOR pathway promotes progestin resistance in endometrial cancer cells by inhibition of autophagy.OncoTargets and therapy · 2017Article
- Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies.American journal of medical genetics. Part C, Seminars in medical genetics · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GTPases and kinases are two predominant signaling modules that regulate cell fate. Dysregulation of Ras, a GTPase, and the three eponymous kinases that form key nodes of the associated phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K)/AKT/mTOR pathway have been implicated in many cancers, including pancreatic cancer, a disease noted for its current lack of effective therapeutics. The K-Ras isoform of Ras is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC) and there is growing evidence linking aberrant PI3K/AKT/mTOR pathway activity to PDAC. Although these observations suggest that targeting one of these nodes might lead to more effective treatment options for patients with pancreatic and other cancers, the complex regulatory mechanisms and the number of sequence-conserved isoforms of these proteins have been viewed as significant barriers in drug development. Emerging insights into the allosteric regulatory mechanisms of these proteins suggest novel opportunities for development of selective allosteric inhibitors with fragment-based drug discovery (FBDD) helping make significant inroads. The fact that allosteric inhibitors of Ras and AKT are currently in pre-clinical development lends support to this approach. In this article, we will focus on the recent advances and merits of developing allosteric drugs targeting these two inter-related signaling pathways.
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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.