Current state and future challenges for PI3K inhibitors in cancer therapy

Marianna Sirico; Alberto D'Angelo; Caterina Gianni; Chiara Casadei; Michela Palleschi; Ugo De Giorgi

doi:10.3390/cancers15030703

Current state and future challenges for PI3K inhibitors in cancer therapy

Marianna Sirico, Alberto D'Angelo, Caterina Gianni, Chiara Casadei, Michela Palleschi, Ugo De Giorgi

Department of Life Sciences

Research output: Contribution to journal › Review article › peer-review

18 Citations (SciVal)

Abstract

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.

Original language	English
Article number	703
Journal	Cancers
Volume	15
Issue number	3
Early online date	23 Jan 2023
DOIs	https://doi.org/10.3390/cancers15030703
Publication status	Published - 28 Feb 2023

Bibliographical note

Funding Information:
This work was partly supported by “Ricerca Corrente”, by the Italian Ministry of Health within the research line "Precision, gender and ethnicity-based medicine and geroscience: genetic-molecular mechanisms in the development, characterization”.

Keywords

PI3K inhibitors
clinical trial
mutations
target therapy

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers15030703Licence: CC BY

Cite this

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abstract = "The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.",

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AU - Sirico, Marianna

AU - D'Angelo, Alberto

AU - Gianni, Caterina

AU - Casadei, Chiara

AU - Palleschi, Michela

AU - De Giorgi, Ugo

N1 - Funding Information: This work was partly supported by “Ricerca Corrente”, by the Italian Ministry of Health within the research line "Precision, gender and ethnicity-based medicine and geroscience: genetic-molecular mechanisms in the development, characterization”.

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N2 - The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.

AB - The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.

KW - PI3K inhibitors

KW - clinical trial

KW - mutations

KW - target therapy

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U2 - 10.3390/cancers15030703

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ER -

Current state and future challenges for PI3K inhibitors in cancer therapy

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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