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KRAS-Mutant Lung Cancers in the Era of Targeted Therapy

  • Jarushka Naidoo
  • Alexander DrilonEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

KRAS mutation Lung cancer Lung adenocarcinoma Erlotinib resistance Targeted therapy MEK inhibition Selumetinib PI3K inhibition mTOR inhibition Hsp90 inhibition 

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Medicine, Thoracic Oncology ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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