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


CONCLUSIONS
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.


CONCLUSIONS
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.
Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
Christine
C
Koch
Joerg
J
Trojan
D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D053842:Microsatellite Instability; D009154:Mutation; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C491743:MET protein, human; C482119:BRAF protein, human