How to manage KRAS G12C-mutated advanced non-small-cell lung cancer.

Autor:	Ricciuti B; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Mira A; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy., Andrini E; Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi University Hospital, ENETS Center of Excellence, Bologna, Italy.; Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Scaparone P; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy., Michelina SV; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy., Pecci F; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Cantini L; Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., De Giglio A; Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi University Hospital, ENETS Center of Excellence, Bologna, Italy.; Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Lamberti G; Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi University Hospital, ENETS Center of Excellence, Bologna, Italy.; Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Ambrogio C; Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy., Metro G; Medical Oncology, Santa Maria Della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Jazyk:	angličtina
Zdroj:	Drugs in context [Drugs Context] 2022 Nov 16; Vol. 11. Date of Electronic Publication: 2022 Nov 16 (Print Publication: 2022).
DOI:	10.7573/dic.2022-7-4
Abstrakt:	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. Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/10/dic.2022-7-4-COI.pdf (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.)
Databáze:	MEDLINE
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