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Inhibition of Tumor Angiogenesis in GIST Therapy

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Tumor Angiogenesis

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Abstract

Gastrointestinal stromal tumors (GISTs) are rare tumors accounting 10–15 new cases/year per million individuals and only represent 2–3% to all gastrointestinal malignancies. They usually arise from the stomach, less frequently from the small bowel, rectum, and esophagus. The hallmark of GISTs is the presence of activating mutations in KIT or platelet-derived growth factor-alpha (PDGFRA) genes, which are considered key drivers in the molecular pathogenesis and that represent important predictive factors. Before the angiogenic inhibition era, GIST was found to be resistant to cytotoxic chemotherapeutic agents. The introduction of small molecules able to inhibit angiogenesis and tumor growth has utterly changed the clinical history of this rare tumor. GISTs have represented for years a model for anti-angiogenic treatment in solid cancer. Tyrosine kinase inhibitors against pro-angiogenic targets, such as imatinib, sunitinib, and regorafenib, are currently available in GIST treatment. One of the main concerns with this molecular therapy is acquired resistance due to a huge variety of factors, including activation of parallel angiogenic pathways. A second important aspect in learning curve of tyrosine kinase inhibitor mechanism of action is the different toxicity profile compared to cytotoxic chemotherapy.

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Author information

Authors and Affiliations

  1. Sarcoma Unit, Royal Marsden Hospital, NHS Foundation, London, UK

    Charlotte Benson & Michela Libertini

Authors
  1. Charlotte Benson
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  2. Michela Libertini
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Correspondence to Charlotte Benson .

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Editors and Affiliations

  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

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Benson, C., Libertini, M. (2019). Inhibition of Tumor Angiogenesis in GIST Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_19

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