Molecular mechanism of gastrointestinal stromal tumors and progress in drug research.
- Author:
Jian LI
1
Author Information
1. Department of GI Oncology, Peking University Cancer Hospital, Beijing 100142, China. oncogene@163.com.
- Publication Type:Journal Article
- MeSH:
Benzimidazoles;
therapeutic use;
Exons;
Gastrointestinal Stromal Tumors;
drug therapy;
genetics;
High-Throughput Nucleotide Sequencing;
Humans;
Imatinib Mesylate;
Mutation;
Piperidines;
Protein Kinase Inhibitors;
therapeutic use;
Proto-Oncogene Proteins c-kit;
genetics;
Pyrimidines;
therapeutic use;
Quinolones;
therapeutic use;
Succinate Dehydrogenase;
genetics;
Sulfonamides
- From:
Chinese Journal of Gastrointestinal Surgery
2016;19(11):1316-1320
- CountryChina
- Language:Chinese
-
Abstract:
The functional mutation of c-kit and platelet-derived growth factor receptor α (PDGFRA) which encode proto-oncogene receptor tyrosine kinase are the crucial pathogeneses of gastrointestinal stromal tumors(GISTs). 80%-85% c-kit gene mutation including exon 11,exon 9,exon 13,exon 17 and 5%-10% PDGFRA gene mutation such as exon 18, exon 12 are examined in GISTs. Neither of c-kit or PDGFRA gene mutation are called wide type GISTs. The pathogeneses of wild type GISTs are not clear. The deficiency of succinate dehydrogenase B(SDHB)-related insulin-like growth factor 1(IGF-1R) activation, BRAF gene mutation and neurofibromatosis type 1 may be related to progression of wild type GISTs. More than half of metastatic GISTs patients receiving imatinib treatment can develop to c-kit secondary mutations, which are responsible for secondary resistance. However, the reasons of imatinib resistance in GISTs without c-kit secondary mutation need to be explored. At present, many clinical trials are ongoing to evaluate new drugs in GISTs treatment, including nilotinib, masitinib, pazopanib, dovitinib, ponatinib, dasatinib, crenolanib, linsitinib and immunotherapy, which may bring resistance GISTs treatment to new hope. Next generation sequencing (NGS) and liquid biopsy will be very important in GISTs research and clinical practice.
