Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Sep:137:57-68.
doi: 10.1016/j.ejca.2020.06.023. Epub 2020 Jul 31.

KRAS inhibition in non-small cell lung cancer: Past failures, new findings and upcoming challenges

Francesco Passiglia  1 , Umberto Malapelle  2 , Marzia Del Re  3 , Luisella Righi  4 , Fabio Pagni  5 , Daniela Furlan  6 , Romano Danesi  7 , Giancarlo Troncone  8 , Silvia Novello  9
Affiliations
Review

KRAS inhibition in non-small cell lung cancer: Past failures, new findings and upcoming challenges

Francesco Passiglia et al. Eur J Cancer. 2020 Sep.

Abstract

Despite the high prevalence of Kirsten rat sarcoma (KRAS) mutations in non-small cell lung cancer (NSCLC), for a long time it has been defined as an 'undruggable target', with precision medicine not considered as an adequate approach to treat this subgroup of patients. After several years of efforts, preliminary data from early clinical trials have recently demonstrated that direct pharmacological inhibition of KRAS p.G12C mutation is possible, emerging as an effective targeted treatment for about 10-12% of patients with advanced NSCLC, with potential relevant impact on their long-term survival and quality of life. This review reports the current status of KRAS mutations detection in the Italian real-word scenario, summarises the biological basis of KRAS inhibition in NSCLC and provides an updated overview of therapeutic strategies, discussing the potential reasons for past failures and analysing the upcoming challenges related to the advent of new targeted agents in clinical practice.

Keywords: AMG510; G12C; KRAS; Lung cancer; Target therapy.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement F.P. reports receiving consultant's fee from MSD and Astra Zeneca; U.P. reports receiving speaker bureau/advisor's fee from Boehringer Ingelheim, AstraZeneca, Roche, MSD, Amgen and Merck; M.D.R. reports receiving speaker bureau/consultant's fee from Astellas, Astra Zeneca, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi-Aventis and Ipsen; L.R. reports receiving consultant's fee from Astra Zeneca, Novartis and Boehringer Ingelheim; R.D. reports receiving speaker bureau/advisor's fee from Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead and EUSA Pharma; G.T. reports receiving speaker bureau/advisor's fee from Roche, MSD, Pfizer and Bayer; S.N. declared speaker bureau/advisor's fee from Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, Astra Zeneca and Boehringer Ingelheim. The other authors have no conflict to declare.

MeSH terms

Substances

LinkOut - more resources