New targets and therapies for gastrointestinal stromal tumors
| Autor: | Agnieszka Wozniak, Yemarshet K. Gebreyohannes, Patrick Schöffski, Maria Debiec-Rychter |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Stromal cell Somatic cell Gastrointestinal Stromal Tumors Platelet-Derived Growth Factor Receptor Alpha medicine.medical_treatment Antineoplastic Agents PDGFRA Receptor tyrosine kinase Targeted therapy 03 medical and health sciences 0302 clinical medicine Medicine Animals Humans Pharmacology (medical) Molecular Targeted Therapy Protein Kinase Inhibitors Gastrointestinal Neoplasms biology GiST business.industry digestive system diseases respiratory tract diseases 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Drug Design Mutation biology.protein Cancer research Immunotherapy business Tyrosine kinase |
| Zdroj: | Expert review of anticancer therapy. 17(12) |
| ISSN: | 1744-8328 |
| Popis: | The majority of gastrointestinal stromal tumors (GIST) are driven by an abnormal receptor tyrosine kinase (RTK) signaling, occurring mainly due to somatic mutations in KIT or platelet derived growth factor receptor alpha (PDGFRA). Although the introduction of tyrosine kinase inhibitors (TKIs) has revolutionized therapy for GIST patients, with time the vast majority of them develop TKI resistance. Advances in understanding the molecular background of GIST resistance allows for the identification of new targets and the development of novel strategies to overcome or delay its occurrence. Areas covered: The focus of this review is on novel, promising therapeutic approaches to overcome heterogeneous resistance to registered TKIs. These approaches involve new TKIs, including drugs specific for a mutated form of KIT/PDGFRA, drugs with inhibitory effect against multiple RTKs, compounds targeting dysregulated downstream signaling pathways, drugs affecting KIT expression and degradation, inhibitors of cell cycle, and immunotherapeutics. Expert commentary: As the resistance to standard TKI treatment can be heterogeneous, a combinational approach for refractory GIST could be beneficial. Moreover, the understanding of the molecular background of resistant disease would allow development of a more personalized approach for these patients and their response to targeted therapy could be monitored closely using 'liquid biopsy'. |
| Databáze: | OpenAIRE |
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