Biomarkers downstream of RAS: a search for robust transcriptional targets.

Balazs Györffy, Reinhold Schäfer

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

The small GTP-binding proteins HRAS, KRAS and NRAS belong to a family of oncoproteins associated with many types of human cancer. Signal transduction processes initiated at receptor tyrosine kinases converge on RAS proteins which serve as molecular switches linking upstream signals with the transcriptional machinery. RAS proteins interact with a number of effector proteins that in turn activate the Raf/MEK/ERK pathway, the PI3K/PKB/Akt pathway, the RalGDS/Ral pathway and other downstream pathways. Mutations in RAS lock the protein in its active form. Chronic activation of the KRAS isoform is the basis for resistance toward antibody therapies targeting receptor tyrosine kinases, as an upstream stimulus through growth factor receptor-mediated activation is no longer required. However, the complexity of the RAS signaling system necessitates the search for additional activating mechanisms as well as biomarkers associated with pathway activation. During recent years, several RAS pathway-related gene signatures were identified, mostly by microarray-based gene expression profiling of normal versus RAS-transformed cells. The signatures can serve as a source of common biomarkers indicating functionally relevant downstream effects of the RAS signaling system. In searching for new markers, we compared the gene expression signatures compiled in 24 independent studies. We analyzed differentially regulated genes recovered in microarray studies on human specimens to discriminate paired normal and tumor tissues. Although the overlap between individual studies was low, this meta-analysis revealed Kruppel-like factor 5 (KLF5), the CD44 antigen and members of the epidermal growth factor (EGR)-family as common downstream effectors of RAS.

Original languageEnglish
Pages (from-to)858-868
Number of pages11
JournalCurrent cancer drug targets
Volume10
Issue number8
Publication statusPublished - Dec 2010

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

Fingerprint Dive into the research topics of 'Biomarkers downstream of RAS: a search for robust transcriptional targets.'. Together they form a unique fingerprint.

  • Cite this