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How to manage KRAS G12C-mutated advanced non-small-cell lung cancer
Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been con...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioExcel Publishing Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677952/ https://www.ncbi.nlm.nih.gov/pubmed/36452878 http://dx.doi.org/10.7573/dic.2022-7-4 |
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author | Ricciuti, Biagio Mira, Alessia Andrini, Elisa Scaparone, Pietro Michelina, Sandra Vietti Pecci, Federica Cantini, Luca De Giglio, Andrea Lamberti, Giuseppe Ambrogio, Chiara Metro, Giulio |
author_facet | Ricciuti, Biagio Mira, Alessia Andrini, Elisa Scaparone, Pietro Michelina, Sandra Vietti Pecci, Federica Cantini, Luca De Giglio, Andrea Lamberti, Giuseppe Ambrogio, Chiara Metro, Giulio |
author_sort | Ricciuti, Biagio |
collection | PubMed |
description | Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC. |
format | Online Article Text |
id | pubmed-9677952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioExcel Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-96779522022-11-29 How to manage KRAS G12C-mutated advanced non-small-cell lung cancer Ricciuti, Biagio Mira, Alessia Andrini, Elisa Scaparone, Pietro Michelina, Sandra Vietti Pecci, Federica Cantini, Luca De Giglio, Andrea Lamberti, Giuseppe Ambrogio, Chiara Metro, Giulio Drugs Context Review Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-cell lung cancer (NSCLC) activating KRAS mutations occur in ~30% of cases, and the glycine to cysteine substitution at codon 12 (G12C) is the most common KRAS alteration. Although KRAS mutations have been considered undruggable for over 40 years, the recent discovery of allelic-specific KRAS inhibitors has paved the way to personalized cancer medicine for patients with tumours harbouring these mutations. Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD-(L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options. We also explore the possible mechanisms of resistance to KRAS inhibition and strategies to overcome resistance in patients with KRAS G12C-mutant NSCLC. BioExcel Publishing Ltd 2022-11-16 /pmc/articles/PMC9677952/ /pubmed/36452878 http://dx.doi.org/10.7573/dic.2022-7-4 Text en Copyright © 2022 Ricciuti B, Mira A, Andrini E, Scaparone P, Vietti Michelina S, Pecci F, Cantini L, De Giglio A, Lamberti G, Ambrogio C, Metro G. https://creativecommons.org/licenses/by-nc-nd/4.0/Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0, which allows anyone to copy, distribute and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission. |
spellingShingle | Review Ricciuti, Biagio Mira, Alessia Andrini, Elisa Scaparone, Pietro Michelina, Sandra Vietti Pecci, Federica Cantini, Luca De Giglio, Andrea Lamberti, Giuseppe Ambrogio, Chiara Metro, Giulio How to manage KRAS G12C-mutated advanced non-small-cell lung cancer |
title | How to manage KRAS G12C-mutated advanced non-small-cell lung cancer |
title_full | How to manage KRAS G12C-mutated advanced non-small-cell lung cancer |
title_fullStr | How to manage KRAS G12C-mutated advanced non-small-cell lung cancer |
title_full_unstemmed | How to manage KRAS G12C-mutated advanced non-small-cell lung cancer |
title_short | How to manage KRAS G12C-mutated advanced non-small-cell lung cancer |
title_sort | how to manage kras g12c-mutated advanced non-small-cell lung cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677952/ https://www.ncbi.nlm.nih.gov/pubmed/36452878 http://dx.doi.org/10.7573/dic.2022-7-4 |
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