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

Ronald P. Dematteo, Michael Heinrich, Wa'el M. El-Rifai, George Demetri

    Research output: Contribution to journalArticle

    529 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 - 2002

    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; El-Rifai, Wa'el M.; Demetri, George.

    In: Human Pathology, Vol. 33, No. 5, 2002, p. 466-477.

    Research output: Contribution to journalArticle

    Dematteo, Ronald P. ; Heinrich, Michael ; El-Rifai, Wa'el M. ; 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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