Management of malignant gastrointestinal stromal tumours

Lancet Oncol. 2002 Nov;3(11):655-64. doi: 10.1016/s1470-2045(02)00899-9.


Gastrointestinal stromal tumours (GISTs) are the most common form of mesenchymal tumour of the gastrointestinal tract. Clinically, they range from small indolent tumours curable with surgery alone to aggressive cancers. Making a distinction between an indolent and a malignant GIST is unreliable with conventional histopathological techniques. The presence of metastases at the time of diagnosis confirms malignancy, but all GISTs should be regarded as having malignant potential. GISTs characteristically express the KIT protein, a transmembrane tyrosine kinase receptor for stem-cell factor. Most GISTs have a mutation in the KIT proto-oncogene that translates into a gain-of-function constitutive activation of the KIT kinase. KIT activation seems to be an early tumour-promoting event in pathogenesis. Commonly, malignant GISTs show high-level primary resistance to conventional chemotherapy. Imatinib mesylate is an orally administered selective inhibitor of certain tyrosine kinases including KIT. Most patients with advanced malignant GISTs achieve clinical benefit and significant antitumour responses with imatinib mesylate. Responses have been durable, and most patients tolerate the drug well at clinically effective doses. Imatinib mesylate is the first effective systemic therapy for advanced GIST.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Benzamides
  • Biomarkers, Tumor
  • Combined Modality Therapy
  • Diagnosis, Differential
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / surgery
  • Humans
  • Imatinib Mesylate
  • Immunohistochemistry
  • Mesoderm / immunology
  • Mesoderm / pathology*
  • Oncogene Proteins / analysis
  • Oncogene Proteins / biosynthesis
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-kit
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Radiotherapy, Adjuvant
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Sarcoma / surgery


  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • MAS1 protein, human
  • Oncogene Proteins
  • Piperazines
  • Proto-Oncogene Mas
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit