Kras-mutant lung cancers in the era of targeted therapy

Jarushka Naidoo, Alexander Drilon

Research output: Contribution to journalArticlepeer-review

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 PBK/mTOR inhibition, the face of targeted therapeutics for this genomic subset of patients is slowly beginning to change.

Original languageEnglish (US)
Pages (from-to)155-178
Number of pages24
JournalAdvances in experimental medicine and biology
Volume893
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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