Current management of succinate dehydrogenase–deficient gastrointestinal stromal tumors
Autor: | Kevin Porras, Mayra Yerba, Paul T. Fanta, Jason K. Sicklick, Pushpa Neppala, Adam M. Burgoyne, Sudeep Banerjee |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research Stromal cell Gastrointestinal Stromal Tumors macromolecular substances PDGFRA medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Animals Humans Medicine neoplasms Gastrointestinal Neoplasms biology GiST business.industry Succinate dehydrogenase Standard treatment digestive system diseases Succinate Dehydrogenase 030104 developmental biology Oncology 030220 oncology & carcinogenesis Localized disease Mutation biology.protein Cancer research business Carcinogenesis Tyrosine kinase |
Zdroj: | Cancer Metastasis Rev |
ISSN: | 1573-7233 0167-7659 |
Popis: | Gastrointestinal stromal tumors (GISTs) are increasingly recognized as having diverse biology. With the development of tyrosine kinase inhibitors molecularly matched to oncogenic KIT and PDGFRA mutations, GISTs have become a quintessential model for precision oncology. However, about 5-10% of GIST lack these driver mutations and are deficient in succinate dehydrogenase (SDH), an enzyme that converts succinate to fumarate. SDH deficiency leads to accumulation of succinate, an oncometabolite that promotes tumorigenesis. SDH-deficient GISTs are clinically unique in that they generally affect younger patients and are associated with GIST-paraganglioma hereditary syndrome, also known as Carney-Stratakis Syndrome. SDH-deficient GISTs are generally resistant to tyrosine-kinase inhibitors, the standard treatment for advanced or metastatic GIST. Thus, surgical resection is the mainstay of treatment for localized disease, but recurrence is common. Clinical trials are currently underway investigating systemic agents for treatment of advanced SDH-deficient GIST. However, further studies are warranted to improve our understanding of SDH-deficient GIST disease biology, natural history, surgical approaches, and novel therapeutics. |
Databáze: | OpenAIRE |
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