Proteogenomics for the Study of Gastrointestinal Stromal Tumors.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain-of-function mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) drive most GISTs, and 85 % of GISTs also contain oncogenic mutations in one of two receptor tyrosine kinases. The advent of tyrosine kinase inhibitors has had a significant impact on the clinical practices for GISTs. However, tumors in more than 80 % of GIST patients acquire resistance against treatments with tyrosine kinase inhibitors; thus, driver mechanisms of secondary resistance as well as biomarkers for early detection of recurrence have been explored for better clinical outcomes. Proteomics is a versatile and straightforward approach to finding the molecular basis of malignancies as well as the innovative seeds for clinical applications. Comprehensive genome, epigenome, and transcriptome data have already been obtained and examined together in GISTs, and proteome data has a unique additional value in multi-omics studies. Various types of samples were examined using proteomics modalities in GIST, suggest the promising utility of proteomic approaches.
Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. takondo@ncc.go.jo.
Tadashi
T
Kondo
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017077:Culture Media, Conditioned / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D000071696:Proteogenomics / Q000379:methods*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
Biomarker; GIST; Gastrointestinal stromal tumor; Molecular targeting drug