Clinical management of gastrointestinal stromal tumors: Before and after STI-571

Ronald P. Dematteo, Michael C. Heinrich, Wael El-Rifai, George Demetri

Research output: Contribution to journalArticle

526 Citations (Scopus)

Abstract

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Until recently, surgery has been the only effective therapy for GIST. However, even after complete resection of tumor, many patients still eventually die of disease recurrence. Conventional chemotherapy and radiation therapy have been of limited value. Within the last few years, it was discovered that most GISTs have a gain-of-function mutation in the c-kit proto-oncogene. This results in ligand-independent activation of the KIT receptor tyrosine kinase and an unopposed stimulus for cell growth. STI-571 is a small molecule that selectively inhibits the enzymatic activity of the ABL, platelet-derived growth factor receptor, and KIT tyrosine kinases and the BCR-ABL fusion protein and is a landmark development in cancer therapy. Its clinical development marks a new era of rational and targeted molecular inhibition of cancer that emanates from direct collaborations between scientists and clinicians. It provides proof of the principle that a specific molecular inhibitor can drastically and selectively alter the survival of a neoplastic cell with a particular genetic aberration. The advent of STI-571 has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST and is also under investigation as a neoadjuvant and adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)466-477
Number of pages12
JournalHuman Pathology
Volume33
Issue number5
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Gastrointestinal Stromal Tumors
Neoplasms
Neoadjuvant Therapy
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases
Gastrointestinal Tract
Radiotherapy
Ligands
Recurrence
Drug Therapy
Mutation
Imatinib Mesylate
Therapeutics
Growth
Proteins

Keywords

  • C-kit proto-oncogene
  • Chemotherapy
  • Gastrointestinal stromal tumor
  • Radiation
  • Sarcoma
  • STI-571
  • Surgery
  • Therapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clinical management of gastrointestinal stromal tumors : Before and after STI-571. / Dematteo, Ronald P.; Heinrich, Michael C.; El-Rifai, Wael; Demetri, George.

In: Human Pathology, Vol. 33, No. 5, 01.01.2002, p. 466-477.

Research output: Contribution to journalArticle

Dematteo, Ronald P. ; Heinrich, Michael C. ; El-Rifai, Wael ; Demetri, George. / Clinical management of gastrointestinal stromal tumors : Before and after STI-571. In: Human Pathology. 2002 ; Vol. 33, No. 5. pp. 466-477.
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