Established and Potential Predictive Biomarkers in Gastrointestinal Cancer--c-Kit, Her2, Ras and Beyond

Digestion. 2015;91(4):294-302. doi: 10.1159/000376573. Epub 2015 Apr 30.

Abstract

Background: Gastrointestinal cancers are among the leading causes of cancer-related deaths worldwide. In different tumor types, personalized systemic treatment strategies based upon biomarker-selection were established over the last years. Although there is a flood of targeted agents in clinical development, only a few targeted agents with a predictive biomarker could be established for the treatment of patients with gastrointestinal cancer patients so far.

Summary: Currently, predictive biomarkers for gastrointestinal cancers include Her2 overexpression or amplification (gastroesophageal adenocarcinoma), c-Kit overexpression (gastrointestinal stromal tumors) and RAS wild-type (colorectal cancer). Selection of patients based on these biomarkers allows the efficient use of targeted agents. The presence of a BRAF mutation and/or high microsatellite instability is prognostic and rather a predictive marker in CRC. Promising candidate markers in advanced clinical development are MET amplification in gastroesophageal adenocarcinoma, Met overexpression and high AFP serum levels in hepatocellular carcinoma.

Key message: Biomarker-guided systemic treatment is established in a subset of patients with gastrointestinal cancer. Ongoing clinical trials and further advances in high-throughput technologies will hopefully result in more personalized systemic treatment strategies for these patients in the near future.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Gastrointestinal Neoplasms / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Microsatellite Instability
  • Mutation
  • Predictive Value of Tests
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-kit / analysis
  • Proto-Oncogene Proteins c-met / analysis
  • Proto-Oncogene Proteins p21(ras) / analysis
  • Receptor, ErbB-2 / analysis

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • ERBB2 protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)