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Cited by 2,138PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerAdvanced Breast Cancer Therapies

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

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Glaviano, Antonino, Foo, Aaron S. C., Lam, Hiu Y., Yap, Kenneth C. H., Jacot, William, Jones, Robert H., Eng, Huiyan, Nair, Madhumathy G. +19 more·2023·Molecular Cancer
DOI 10.1186/s12943-023-01827-6PMC PMC10436543
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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.

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  • Inhibition of the PI3K/AKT pathway may be a potential therapeutic for MM.

    “Thus, inhibition the PI3K/AKT pathway may be a potential therapeutic for the treatment of MM [73].”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [73]

    The Conclusion describes PI3K inhibition as a target for antitumor therapy and AKT inhibition as potentially antineoplastic. It does not make that therapeutic claim specifically for MM; the passage mentioning multiple myeloma cells in the Resistance section concerns a response to an mTOR inhibitor, not the proposed PI3K/AKT treatment. (LLM, conf=0.84)

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Authors
Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., Kulke, M. H., Baird, R. D., Prabhu, J. S., Carbone, D., Pecoraro, C., Teh, D. B. L., Sethi, G., Cavalieri, V., Lin, K. H., Javidi-Sharifi, N. R., Toska, E., Davids, M. S., Brown, J. R., Diana, P., Stebbing, J., Fruman, D. A., & Kumar, A. P.
Affiliations
  • University of Palermo (IT)
  • National University of Singapore (SG)
  • Inserm (FR)
  • Velindre Cancer Centre (GB)
  • St.John's Medical College Hospital (IN)
  • Wenzhou Medical University (CN)
  • Boston University (US)
  • Cancer Research UK (GB)
  • Harvard University (US)
  • Johns Hopkins University (US)
  • Imperial College London (GB)
  • University of California, Irvine (US)
Corresponding author
Kumar, Alan P.
ORCID
Venue
Molecular Cancer
Publisher
Springer Science and Business Media LLC
Published
2023-08-18
Volume
22
Issue
1
Pages
138-138
ISSN
1476-4598 (ISSN-L)
DOI
10.1186/s12943-023-01827-6
PMC
PMC10436543
OpenAlex
W4385986528
Cited by
2,138
References
31
Citations by year
2026: 694 · 2025: 955 · 2024: 472 · 2023: 15
FWCI
56.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion, other-oa)
  • HAL (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • National University of Singapore (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Social Science Research Council
  • Alex's Lemonade Stand Foundation for Childhood Cancer
  • Ministry of Education, India
  • Institut Gustave-Roussy
  • National Medical Research Council (A-0006179-00-00)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
Keywords
PI3K/AKT/mTOR pathway, signal transduction, cancer, treatment resistance, PI3K inhibitors, AKT inhibitors, mTOR inhibitors, PTEN loss, combination therapy, immunotherapy
MeSH terms
Humans, Neoplasms, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases

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