title: Biomarkers and novel therapeutic targets in gastrointestinal stromal tumors (GISTs).
abstract: Gastrointestinal stromal tumors (GISTs) owe their development to the activating mutations in mast/stem cell growth factor receptor (KIT) or platelet-derived growth factor receptor A (PDGFRA) oncogenes. Both these KIT and PDGFRA oncogenes are members of the type III transmembrane receptor tyrosine kinase family that stimulates intracellular signaling pathways controlling cell proliferation, adhesion, apoptosis, survival, and differentiation. The presence and type of KIT/PDGFRA mutations help to predict the imatinib mesylate therapy, a selective tyrosine kinase inhibitor. Moreover, there is reported a small proportion of wild-type GISTs for both KIT and PDGFRA genes, and tumors more often acquire secondary mutations on KIT, that results into imatinib resistance. New patents to the GISTs imatinib resistant have recently been introduced. At present, sunitinib, is prescribed as second line therapy for patients with imatinibresistant or imatinib-intolerant GIST, and a number of other drugs, such as masitinib and valatinib, are in the pipeline. The present research focuses on GISTs diagnostic, prognostic and therapeutic biomarkers and addresses the development of novel patents for the treatment of these patients.
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, CEP 14784 400, Barretos, S. Paulo, Brazil.
authors.forename: Nathália C
authors.initials: NC
authors.lastname: Campanella
authors.forename: António T
authors.initials: AT
authors.lastname: de Oliveira
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.forename: Denise P
authors.initials: DP
authors.lastname: Guimarães
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D011237:Predictive Value of Tests; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor