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Clinical development landscape in GIST: from novel agents that target accessory pathways to revisiting non-targeted therapies
- Source :
- Expert Opinion on Investigational Drugs. 26:427-443
- Publication Year :
- 2017
- Publisher :
- Informa UK Limited, 2017.
-
Abstract
- Activating mutations in the genes encoding the tyrosine receptor kinases KIT and platelet-derived growth factor receptor occur in 85%-90% of patients with gastrointestinal stromal tumors (GIST). Although imatinib and other tyrosine kinase inhibitors have revolutionized the treatment of GIST, most patients progress within a few years. Areas covered: Monoclonal antibodies and small-molecule inhibitors targeting specific signaling pathways or proteins associated with resistance to existing treatments are being explored as alternative treatment approaches for GIST. Other alternative approaches include inhibiting more general regulators of protein folding, chromatin packaging, and cell-cycle regulation; nontargeted approaches are also being evaluated in select patient populations. This review summarizes preclinical and clinical data from agents using these accessory pathways. Expert opinion: As we learn more about GIST biology, it is becoming clear that treatment strategies will become more personalized, as reflected by the fact that several trials are enrolling specific subpopulations of patients with GIST. Going forward, researchers should evaluate these new drugs alone or in combination with other types of drugs to better meet patient needs.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Gastrointestinal Stromal Tumors
Antineoplastic Agents
Biology
Bioinformatics
03 medical and health sciences
0302 clinical medicine
Growth factor receptor
medicine
Humans
Receptors, Platelet-Derived Growth Factor
Pharmacology (medical)
Molecular Targeted Therapy
Protein Kinase Inhibitors
PI3K/AKT/mTOR pathway
Gastrointestinal Neoplasms
Pharmacology
GiST
Kinase
Antibodies, Monoclonal
Imatinib
General Medicine
Proto-Oncogene Proteins c-kit
030104 developmental biology
Drug Design
030220 oncology & carcinogenesis
Mutation
Signal transduction
Tyrosine kinase
medicine.drug
Subjects
Details
- ISSN :
- 17447658 and 13543784
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Expert Opinion on Investigational Drugs
- Accession number :
- edsair.doi.dedup.....bb0a5c24462146e7732d043080be2131