Gastrointestinal Stromal Tumor: Current Approaches and Future Directions in the Treatment of Advanced Disease

Hematol Oncol Clin North Am. 2025 Aug;39(4):773-784. doi: 10.1016/j.hoc.2025.04.006. Epub 2025 May 13.

Abstract

This review discusses the current and future landscape of advanced gastrointestinal stromal tumor (GIST) treatment. It covers the role of tyrosine kinase inhibitors (TKIs), specifically imatinib, and further treatment options, such as sunitinib, regorafenib, and ripretinib, as well as avapritinib for platelet-derived growth factor receptor alpha D842V mutations. In addition, this review emphasizes individualized treatment strategies within multidisciplinary expert teams, including surgery and other locoregional therapies, together with the importance of mutation-guided approaches, particularly for wild-type GISTs. Finally, it explores the potential of next-generation KIT inhibitors, combination therapies, and other investigational approaches.

Keywords: Gastrointestinal stromal tumor (GIST); Imatinib; KIT mutation; PDGFRA mutation; Targeted therapy; Tyrosine-kinase inhibitors (TKIs).

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Gastrointestinal Neoplasms* / drug therapy
  • Gastrointestinal Neoplasms* / genetics
  • Gastrointestinal Neoplasms* / pathology
  • Gastrointestinal Neoplasms* / therapy
  • Gastrointestinal Stromal Tumors* / drug therapy
  • Gastrointestinal Stromal Tumors* / genetics
  • Gastrointestinal Stromal Tumors* / metabolism
  • Gastrointestinal Stromal Tumors* / pathology
  • Gastrointestinal Stromal Tumors* / therapy
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors* / therapeutic use
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / genetics

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-kit
  • Antineoplastic Agents
  • Imatinib Mesylate