| Theme | GIST : Current Progress on Diagnosis and Treatment | |
|---|---|---|
| Title | Novel Therapeutic Agents for Imatinib-refractory Gastrointestinal Stromal Tumors (GISTs) | |
| Publish Date | 2010/06 | |
| Author | Masako Asayama | Division of Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East |
| Author | Yasuyuki Kawamoto | Division of Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East |
| Author | Toshihiko Doi | Division of Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East |
| [ Summary ] | Treatment with imatinib, a selective TK inhibitor, induces dramatic clinical benefits in advanced GIST (gastrointestinal stromal tumor) patients. There are certain imatinib-refractory GISTs with particular genotypes. Sunitinib, a broad spectrum TK inhibitor, is effective and approved for imatinib-resistant GISTs. Increasing the dosage of imatinib up to 800 mg daily can be an alternative for patients with KIT exon 9 mutations or low imatinib troughplasma levels. However, GISTs with mutations in TK2, suchas KIT exon 17, 18 or PDGFRα exon 18, are still resistant to both treatments. The development of new approaches for imatinib-resistant GISTs is warranted. New types of TK inhibitors, combination therapy with angiogenesis inhibitors, inhibitors targeting downstream proteins in the KIT and PDGFRα pathways, as well as a treatment to degrade mutated KIT itself, are in clinical trials at this time. | |