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Review
. 2022 Apr 24;13(4):276-286.
doi: 10.5306/wjco.v13.i4.276.

New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2

Maria Eugenia Olmedo  1 , Raquel Cervera  2 , Luis Cabezon-Gutierrez  3 , Yolanda Lage  4 , Elena Corral de la Fuente  5 , Ana Gómez Rueda  4 , Xabier Mielgo-Rubio  6 , Juan Carlos Trujillo  7 , Felipe Couñago  8
Affiliations
Review

New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2

Maria Eugenia Olmedo et al. World J Clin Oncol. .

Abstract

The 2004 discovery of EGFR mutations, followed by ALK rearrangements, ushered in a targeted therapy era for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC. In the last decade, rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies. Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets, including RET, NTRK fusions, c-MET alterations, and activating mutations in KRAS, BRAF, and HER2, all with frequencies greater than 1%. Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development. This review updates the therapeutic arsenal that especially targets those genes.

Keywords: BRAF; HER2; KRAS; MET; NTRK; Non-small cell lung cancer; RET; Targeted therapy; Uncommon mutations.

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Conflict of interest statement

Conflict-of-interest statement: Xabier Mielgo-Rubio declares the following conflicts of interest: Advisory role; Boehringer-Ingelheim, AstraZeneca, Bristol Myers Squibb. Speakers’ bureau; Roche, AstraZeneca, Bristol Myers Squibb, MSD, Abbott. Research funding; Bristol Myers Squibb. Luis Cabezón-Gutiérrez received speaker or consulting fees from Angelini, Grunenthal, Kyowa Kirin, Mundipharma, Pfizer, Roche, Rovi, Leo Pharma, Merck Serono, Ipsen Pharma, Lilly, Amgen, Boehringer Ingelheim, and AstraZeneca; The remaining authors declare no conflicts of interest.

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