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KRAS-Mutant Lung Cancers in the Era of Targeted Therapy

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Book cover Lung Cancer and Personalized Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 893))

Abstract

KRAS-mutant lung cancers account for approximately 25 % of non-small cell lung carcinomas, thus representing an enormous burden of cancer worldwide. KRAS mutations are clear drivers of tumor growth and are characterized by a complex biology involving the interaction between mutant KRAS, various growth factor pathways, and tumor suppressor genes. While KRAS mutations are classically associated with a significant smoking history, they are also identified in a substantial proportion of never-smokers. These mutations are found largely in lung adenocarcinomas with solid growth patterns and tumor-infiltrating lymphocytes. A variety of tools are available for diagnosis including Sanger sequencing, multiplex mutational hotspot profiling, and next-generation sequencing. The prognostic and predictive roles of KRAS status remain controversial. It has become increasingly clear, however, that KRAS mutations drive primary resistance to EGFR tyrosine kinase inhibition. Until recently, mutant KRAS was not thought of as a clinically-targetable driver in lung cancers. With the expansion of our knowledge regarding the biology of KRAS-mutant lung cancers and the role of MEK and PI3K/mTOR inhibition, the face of targeted therapeutics for this genomic subset of patients is slowly beginning to change.

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Authors and Affiliations

  1. Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jarushka Naidoo & Alexander Drilon

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  1. Jarushka Naidoo
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  2. Alexander Drilon
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Correspondence to Alexander Drilon .

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Editors and Affiliations

  1. Wayne State University, Karmanos Cancer Institute, Detroit, Michigan, USA

    Aamir Ahmad

  2. Wayne State University, Karmanos Cancer Institute, Detroit, Michigan, USA

    Shirish Gadgeel

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Naidoo, J., Drilon, A. (2016). KRAS-Mutant Lung Cancers in the Era of Targeted Therapy. In: Ahmad, A., Gadgeel, S. (eds) Lung Cancer and Personalized Medicine. Advances in Experimental Medicine and Biology, vol 893. Springer, Cham. https://doi.org/10.1007/978-3-319-24223-1_8

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