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Cited by 497PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerFOXO transcription factor regulation

The pathogenic role of PI3K/AKT pathway in cancer onset and drug resistance: an updated review

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Rascio, Federica, Spadaccino, Federica, Rocchetti, Maria Teresa, Castellano, Giuseppe, Stallone, Giovanni, Netti, Giuseppe Stefano, Ranieri, Elena·2021·Cancers
DOI 10.3390/cancers13163949PMC PMC8394096
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Abstract

The PI3K/AKT pathway is one of the most frequently over-activated intracellular pathways in several human cancers. This pathway, acting on different downstream target proteins, contributes to the carcinogenesis, proliferation, invasion, and metastasis of tumour cells. A multi-level impairment, involving mutation and genetic alteration, aberrant regulation of miRNAs sequences, and abnormal phosphorylation of cascade factors, has been found in multiple cancer types. The deregulation of this pathway counteracts common therapeutic strategies and contributes to multidrug resistance. In this review, we underline the involvement of this pathway in patho-physiological cell survival mechanisms, emphasizing its key role in the development of drug resistance. We also provide an overview of the potential inhibition strategies currently available.

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  • Resistance to DNA-damaging therapy still exists, as feedback activation of the RAS/MAPK and/or PI3K/AKT/mTOR pathways has often been associated with therapy-resistant cancer.

    “However, resistance to DNA-damaging therapy still exists, as feedback activation of the RAS/MAPK and/or PI3K/AKT/mTOR pathways has often been associated with therapy-resistant cancer [31].”

    From Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer (2024) · cites this paper as [31]

    The Introduction and Section 6 link PI3K/AKT activation to cancer drug resistance, including chemoresistance. Section 7 also describes compensatory activation of other signalling pathways during therapeutic resistance. The cited passages do not establish the more specific claim about feedback activation of RAS/MAPK or resistance to DNA-damaging therapy in particular; page numbers are unavailable in our copy. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Rascio, F., Spadaccino, F., Rocchetti, M. T., Castellano, G., Stallone, G., Netti, G. S., & Ranieri, E.
Affiliations
University of Foggia (IT)
Corresponding author
Rascio, Federica
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2021-08-05
Volume
13
Issue
16
Pages
3949
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers13163949
PMC
PMC8394096
OpenAlex
W3187957129
Cited by
497
References
6
Citations by year
2026: 103 · 2025: 160 · 2024: 136 · 2023: 59 · 2022: 34 · 2021: 5
FWCI
6.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Italian Ministry of Education and University (MIUR) (GR-2016-02362239)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Keywords
PI3K/Akt signaling, cancer, carcinogenesis, drug resistance, multidrug resistance, tumor cell proliferation, metastasis, cell survival signaling, PI3K mutations, microRNA dysregulation, protein phosphorylation, PI3K/AKT inhibitors

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