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The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review

SIMPLE SUMMARY: Drug resistance remains one of the major problems in cancer therapy and is responsible for up to 90% of cancer-related deaths. It exists across all types of cancer and treatment; thus, determining how to overcome this problem is a goal that involves understanding biological mechanism...

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Autores principales: Rascio, Federica, Spadaccino, Federica, Rocchetti, Maria Teresa, Castellano, Giuseppe, Stallone, Giovanni, Netti, Giuseppe Stefano, Ranieri, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394096/
https://www.ncbi.nlm.nih.gov/pubmed/34439105
http://dx.doi.org/10.3390/cancers13163949
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author Rascio, Federica
Spadaccino, Federica
Rocchetti, Maria Teresa
Castellano, Giuseppe
Stallone, Giovanni
Netti, Giuseppe Stefano
Ranieri, Elena
author_facet Rascio, Federica
Spadaccino, Federica
Rocchetti, Maria Teresa
Castellano, Giuseppe
Stallone, Giovanni
Netti, Giuseppe Stefano
Ranieri, Elena
author_sort Rascio, Federica
collection PubMed
description SIMPLE SUMMARY: Drug resistance remains one of the major problems in cancer therapy and is responsible for up to 90% of cancer-related deaths. It exists across all types of cancer and treatment; thus, determining how to overcome this problem is a goal that involves understanding biological mechanisms and also includes clinical trials to test new therapeutic strategies. In this review, we will highlight the emerging role of the PI3K/Akt pathway in drug resistance by discussing recent findings of a multi-level deregulation. Combinational and personalized therapies, which should take this pathway into consideration, might provide better treatment strategies and improved efficacy for fighting drug resistance in cancer. 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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spelling pubmed-83940962021-08-28 The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review Rascio, Federica Spadaccino, Federica Rocchetti, Maria Teresa Castellano, Giuseppe Stallone, Giovanni Netti, Giuseppe Stefano Ranieri, Elena Cancers (Basel) Review SIMPLE SUMMARY: Drug resistance remains one of the major problems in cancer therapy and is responsible for up to 90% of cancer-related deaths. It exists across all types of cancer and treatment; thus, determining how to overcome this problem is a goal that involves understanding biological mechanisms and also includes clinical trials to test new therapeutic strategies. In this review, we will highlight the emerging role of the PI3K/Akt pathway in drug resistance by discussing recent findings of a multi-level deregulation. Combinational and personalized therapies, which should take this pathway into consideration, might provide better treatment strategies and improved efficacy for fighting drug resistance in cancer. 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. MDPI 2021-08-05 /pmc/articles/PMC8394096/ /pubmed/34439105 http://dx.doi.org/10.3390/cancers13163949 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rascio, Federica
Spadaccino, Federica
Rocchetti, Maria Teresa
Castellano, Giuseppe
Stallone, Giovanni
Netti, Giuseppe Stefano
Ranieri, Elena
The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review
title The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review
title_full The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review
title_fullStr The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review
title_full_unstemmed The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review
title_short The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review
title_sort pathogenic role of pi3k/akt pathway in cancer onset and drug resistance: an updated review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394096/
https://www.ncbi.nlm.nih.gov/pubmed/34439105
http://dx.doi.org/10.3390/cancers13163949
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