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Review
. 2021 Dec 16;13(24):6332.
doi: 10.3390/cancers13246332.

Targeting KRAS in NSCLC: Old Failures and New Options for "Non-G12c" Patients

Francesca Jacobs  1 , Massimiliano Cani  1 , Umberto Malapelle  2 , Silvia Novello  1 , Valerio Maria Napoli  1 , Paolo Bironzo  1
Affiliations
Review

Targeting KRAS in NSCLC: Old Failures and New Options for "Non-G12c" Patients

Francesca Jacobs et al. Cancers (Basel). .

Abstract

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.G12C KRAS mutation positive patients is predicted to change soon. This review provides a comprehensive and critical overview of ongoing studies into NSCLC patients with KRAS mutations other than p.G12C and discusses future scenarios that will hopefully change the story of this disease.

Keywords: G12C; KRAS; NSCLC; drug resistance; non-G12C; oncogene; targeted therapy.

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Conflict of interest statement

Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, ThermoFisher Scientifics, Diaceutics, GSK, Merck and AstraZeneca, unrelated to the current work. Paolo Bironzo reports receiving grants from Roche and personal fees from Roche, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Takeda, and BeiGene, unrelated to the current work. Silvia Novello declared speaker bureau/advisor’s fee from Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Astra Zeneca and Boehringer Ingelheim, unrelated to the current work. Francesca Jacobs, Massimiliano Cani and Valerio Maria Napoli have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
RAS pathway and signalling.
Figure 2
Figure 2
Incidence of KRAS mutation subtypes in NSCLC.
See this image and copyright information in PMC

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