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
. 2018 Apr;6(8):142.
doi: 10.21037/atm.2018.04.28.

Beyond EGFR and ALK: targeting rare mutations in advanced non-small cell lung cancer

Stavros Gkolfinopoulos  1 , Giannis Mountzios  2
Affiliations
Review

Beyond EGFR and ALK: targeting rare mutations in advanced non-small cell lung cancer

Stavros Gkolfinopoulos et al. Ann Transl Med. 2018 Apr.

Abstract

Lung cancer remains the leading cause of cancer-related death in men and women, despite its constantly declining rates in incidence and mortality in the developed world. The past decade has witnessed an unprecedented rise in the development of molecular targeted therapies in various types of tumors. In non-small cell lung cancer (NSCLC), the greatest paradigm shift is the implementation of EGFR and ALK tyrosine kinase inhibitors in the first line and subsequent lines of therapy, with impressive results. Though less frequent than the molecular alterations in the aforementioned genes, a number of aberrations in potential oncogenic drivers has been discovered, namely mutations in the genes KRAS, BRAF, HER2, PI3KCA and DDR2, ROS1 and RET rearrangements and MET, HER2 and FGFR1 gene amplifications. A great number of clinical trials are currently underway, evaluating agents specifically designed to target these alterations, with mixed results so far. The greatest cumulative benefit offered by these trials is that, despite their success or failure in their objective goals, they have provided us with a better understanding of the complexity of the molecular intracellular processes, necessitating thus the accurate interpretation of the preclinical data in order to appropriately select the patients that may derive benefit from targeted treatment strategies.

Keywords: BRAF; DDR2; FGFR1; HER2; KRAS; MET; Non-small cell lung cancer (NSCLC); PI3KCA; RET; ROS1; oncogenic drivers.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Siegel R, Ma J, Zou Z, et al. Cancer statistics 2014. CA Cancer J Clin 2014;64:9-29. 10.3322/caac.21208 - DOI - PubMed
    1. Johnson BE, Kris MG, Berry LD, et al. A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: the lung cancer mutation consortium (LCMC). J Clin Oncol 2013;31:abstr 8019.
    1. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 2014;311:1998-2006. 10.1001/jama.2014.3741 - DOI - PMC - PubMed
    1. Marchetti A, Felicioni L, Malatesta S, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011;29:3574-9. 10.1200/JCO.2011.35.9638 - DOI - PubMed
    1. Paik PK, Arcila ME, Fara M, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011;29:2046-51. 10.1200/JCO.2010.33.1280 - DOI - PMC - PubMed