+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Targeted therapies in gastrointestinal stromal tumors



Targeted therapies in gastrointestinal stromal tumors



Seminars in Diagnostic Pathology 25(4): 295-303



The discovery of constitutive KIT activation as the central mechanism of gastrointestinal stromal tumor (GIST) pathogenesis suggested that inhibiting or blocking KIT signaling might be the milestone in the targeted therapy of GISTs. Indeed, imatinib mesylate inhibits KIT kinase activity and represents the front-line drug for the treatment of unresectable and metastatic GISTs. Despite a high rate of response in patients with KIT exon 11 mutated GISTs, the failure rate is significantly higher in patients with a wild-type genotype, suggesting an alternative activated pathway not targeted by imatinib therapy. The most common mechanism of resistance is through polyclonal acquisition of second-site mutations in the kinase domain, which highlights the future therapeutic challenges in salvaging these patients after failing kinase inhibitors monotherapies. This review article summarizes the recent knowledge accumulated on targeted therapy in GIST, based on the central role of KIT oncogenic activation and subsequent signal transduction in the pathogenesis of GIST. In addition, we provide an updated discussion on diagnostic pitfalls, including changes secondary to imatinib response and resistance.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 056119145

Download citation: RISBibTeXText

PMID: 19013895

DOI: 10.1053/j.semdp.2008.08.004


Related references

Gastrointestinal stromal tumors: molecular mechanisms and targeted therapies. Pathology Research International 2011: 708596, 2011

Targeted therapies of gastrointestinal stromal tumors (GIST)--the next frontiers. Biochemical Pharmacology 80(5): 575-583, 2010

Predictors of response to targeted therapies for gastrointestinal stromal tumors. Archives of Pathology and Laboratory Medicine 136(5): 483-489, 2012

Gastrointestinal stromal tumors (GIST): at the forefront of targeted therapies. Medecine Sciences 29(6-7): 630-636, 2013

Implications of mutational analysis for the management of patients with gastrointestinal stromal tumors and the application of targeted therapies. Cancer Investigation 28(8): 839-848, 2010

Novel receptor tyrosine kinase targeted combination therapies for imatinib-resistant gastrointestinal stromal tumors (GIST). Oncotarget 6(4): 1954-1966, 2015

Gastrointestinal stromal tumors A model for understanding solid tumor biology and development of targeted therapies, or just another low-hanging fruit?. Asia-Pacific Journal of Clinical Oncology 4(4): 185-187, 2008

Monitoring the effect of targeted therapies in a gastrointestinal stromal tumor xenograft using a clinical PET/CT. Molecular Imaging and Biology 13(6): 1234-1240, 2012

Gastrointestinal stromal tumors (GIST)--a paradigm of successful targeted therapy of solid tumors. Acta Medica Croatica 60(5): 471-475, 2007

New targets and therapies for gastrointestinal stromal tumors. Expert Review of Anticancer Therapy 17(12): 1117-1129, 2017

How to decide whether to offer and use "nonstandard" therapies in patients with advanced sarcomas and gastrointestinal stromal tumors: global variations in clinical practice, assessment, and access to therapies in diseases with limited incidence and data. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting 2012: 645-650, 2012

Treatments for gastrointestinal stromal tumors that are resistant to standard therapies. Future Oncology 10(13): 2045-2059, 2015

Dual energy CT for monitoring targeted therapies in patients with advanced gastrointestinal stromal tumor: initial results. Current Pharmaceutical Biotechnology 12(4): 547-557, 2011

Dual Energy Ct for Monitoring Targeted Therapies in Patients with Advanced Gastrointestinal Stromal Tumor: Initial Results. Current Pharmaceutical Biotechnology 12(4): 547-557, 2011

Gastrointestinal neuroendocrine tumors: a role for targeted therapies?. Endocrine-Related Cancer 14(2): 207-219, 2007