Evidence mapPaperPMID 37596643Full record

ReviewMolecular cancer2023

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.

Antonino Glaviano, Aaron S C Foo, Hiu Y Lam, Kenneth C H Yap, William Jacot, Robert H Jones, Huiyan Eng, Madhumathy G Nair, Pooyan Makvandi, Birgit Geoerger and 17 more

Open access · goldAbstract readReview
In one paragraph

Review in Molecular cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,206 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,206citing papers in PubMed, 1 pooled it
265.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1,206 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,724 citations in OpenAlex.

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  20. Coordination-controlled photophysics and antiproliferative activity of coumarin-linked schiff bases and Zn(II) complexes.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026
    Article

1,146 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 12 institutions in 7 countries.

Antonino GlavianoDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, Italy.
Aaron S C FooDepartment of Surgery, National University Hospital Singapore, National University of Singapore, Singapore, Singapore.
Hiu Y LamDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
Kenneth C H YapDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
William JacotDepartment of Medical Oncology, Institut du Cancer de Montpellier, Inserm U1194, Montpellier University, Montpellier, France.
Robert H JonesCardiff University and Velindre Cancer Centre, Museum Avenue, Cardiff, CF10 3AX, UK.
Huiyan EngDepartment of Surgery, National University Hospital Singapore, National University of Singapore, Singapore, Singapore.
Madhumathy G NairDivision of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore, 560034, India.
Pooyan MakvandiThe Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, Zhejiang, China.
Birgit GeoergerDepartment of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Center, Inserm U1015, Université Paris-Saclay, Paris, France.
Matthew H KulkeSection of Hematology and Medical Oncology, Boston University and Boston Medical Center, Boston, MA, USA.
Richard D BairdCancer Research UK Cambridge Centre, Hills Road, Cambridge, CB2 0QQ, UK.
Jyothi S PrabhuDivision of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore, 560034, India.
Daniela CarboneDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, Italy.
Camilla PecoraroDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, Italy.
Daniel B L TehDepartments of Ophthalmology and Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, and Neurobiology Programme, National University of Singapore, Singapore, Singapore.
Gautam SethiDepartment of Surgery, National University Hospital Singapore, National University of Singapore, Singapore, Singapore.
Vincenzo CavalieriDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, Italy.
Kevin H LinDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nathalie R Javidi-SharifiDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Eneda ToskaDepartment of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
Matthew S DavidsDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jennifer R BrownDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Patrizia DianaDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90123, Palermo, Italy.
Justin StebbingDivision of Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
David A FrumanDepartment of Molecular Biology and Biochemistry, University of California, 216 Sprague Hall, Irvine, CA, USA.
Alan P KumarDepartment of Surgery, National University Hospital Singapore, National University of Singapore, Singapore, Singapore. apkumar@nus.edu.sg.
National University of Singapore · SGUniversity of Palermo · ITHarvard University · USInserm · FRSt.John's Medical College Hospital · INBoston University · USCancer Research UK Cambridge Center · GBHammersmith Hospital · GBJohns Hopkins University · USUniversity of California, Irvine · USVelindre Cancer Centre · GBWenzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

Indexed as

NeoplasmsPhosphatidylinositol 3-KinasesHumansProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAKT inhibitorsAllosteric mTOR inhibitorsATP-competitive mTOR inhibitorsBi-steric mTOR inhibitorsCancerDual PI3K/mTOR inhibitorsIsoform-specific PI3K inhibitorsPan PI3K inhibitorsPDK1 inhibitorsPI3K/AKT/mTORC pathway

Identifiers

PMID37596643
PMCPMC10436543
OpenAlexW4385986528

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.