Gastric Cancer

, Volume 12, Issue 4, pp 175–188

Gastrointestinal stromal tumor: a bridge between bench and bedside

  • Toshirou Nishida
  • Tsuyoshi Takahashi
  • Yasuaki Miyazaki
Review Article

DOI: 10.1007/s10120-009-0525-8

Cite this article as:
Nishida, T., Takahashi, T. & Miyazaki, Y. Gastric Cancer (2009) 12: 175. doi:10.1007/s10120-009-0525-8

Abstract

Gastrointestinal stromal tumor (GIST) is considered to be driven by a gain-of-function mutation in the KIT or PDGFRA gene. Cure can be obtained only by complete surgical removal of the GIST; however, imatinib, an inhibitor of KIT and PDGFRA, is indicated for advanced, recurrent, and/or metastatic GISTs. Imatinib exhibited remarkable clinical effects on advanced GISTs, with substantial tolerability. Its efficacy greatly depends on the genotype of GIST. The drug, however, met intrinsic or acquired resistance during the treatment, of which the molecular mechanisms were mostly dependent on the genotype of GIST, including primary mutations or secondary mutations in the kinase domains of the corresponding target genes, respectively. Although sunitinib had substantial effects on imatinib-resistant GIST, this drug also encountered primary or secondary resistance depending on the genotype. Thus, advanced GIST may require multidisciplinary treatment. Because resistance mechanisms show some regularity, it is hoped that, in the near future, we may be able to develop a new drug to which resistance does not occur easily, based on scientific evidence.

Key words

KIT PDGFRA Imatinib Sunitinib Resistance 
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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2009

Authors and Affiliations

  • Toshirou Nishida
    • 1
    • 2
  • Tsuyoshi Takahashi
    • 2
    • 3
  • Yasuaki Miyazaki
    • 2
  1. 1.Department of SurgeryOsaka Police HospitalOsakaJapan
  2. 2.Department of SurgeryOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of SurgeryOsaka General Medical CenterOsakaJapan