Gastrointestinal stromal tumour

Summary Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the gastrointestinal tract and are highly resistant to conventional chemotherapy and radiotherapy. Such tumours usually have activating mutations in either KIT (75–80%) or PDGFRA (5–10%), two closely related recepto...

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Bibliographic Details
Published inThe Lancet (British edition) Vol. 369; no. 9574; pp. 1731 - 1741
Main Authors Rubin, Brian P, MD, Heinrich, Michael C, Prof, Corless, Christopher L, Prof
Format Journal Article
LanguageEnglish
Published London Elsevier Ltd 19.05.2007
Lancet
Elsevier Limited
Subjects
Antineoplastic Agents - therapeutic use
Benzamides
Biological and medical sciences
Cancer
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gastrointestinal diseases
Gastrointestinal Stromal Tumors - drug therapy
Gastrointestinal Stromal Tumors - genetics
Gastrointestinal Stromal Tumors - mortality
Gastrointestinal tract
General aspects
Genetics
Humans
Imatinib Mesylate
Indoles - therapeutic use
Internal Medicine
Kinases
Male
Medical sciences
Middle Aged
Molecular Biology
Mutation
Piperazines - therapeutic use
Positron-Emission Tomography
Proteins
Pyrimidines - therapeutic use
Pyrroles - therapeutic use
Randomized Controlled Trials as Topic
Risk Assessment
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Studies
Tumors
Medicine
Digestive diseases
Gastrointestinal stromal tumor
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Summary:Summary Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the gastrointestinal tract and are highly resistant to conventional chemotherapy and radiotherapy. Such tumours usually have activating mutations in either KIT (75–80%) or PDGFRA (5–10%), two closely related receptor tyrosine kinases. These mutations lead to ligand-independent activation and signal transduction mediated by constitutively activated KIT or PDGFRA. Targeting these activated proteins with imatinib mesylate, a small-molecule kinase inhibitor, has proven useful in the treatment of recurrent or metastatic gastrointestinal stromal tumours and is now being tested as an adjuvant or neoadjuvant. However, resistance to imatinib is a growing problem and other targeted therapeutics such as sunitinib are available. The important interplay between the molecular genetics of gastrontestinal stromal tumour and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumours.
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ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(07)60780-6