Targeted therapy

Biology

Stromal tumor

Stromal cell

Receptor

GiST

Receptor tyrosine kinase

Cancer research

Myeloid leukemia

Sunitinib

Imatinib mesylate

Bioinformatics

Imatinib

Tyrosine kinase

Tyrosine-kinase inhibitor

Internal medicine

PDGFRA

Oncology

Medicine

Cancer

American Society of Clinical Oncology Educational Book

Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin and a compelling clinical and biologic model for the rational development of molecularly targeted agents. This is because the majority of GISTs are driven by gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases. Specific GIST mutations circumscribe well-defined molecular subgroups that must be determined during the diagnostic work-up to guide clinical management, including therapeutic decisions. Surgery is the cornerstone treatment in localized disease and can also be clinically relevant in the metastatic setting. The correct combination and sequence of targeted agents and surgical procedures improves outcomes for patients with GIST and should be discussed individually within multidisciplinary expert teams. All currently approved agents for the treatment of GIST are based on orally available tyrosine kinase inhibitors targeting KIT and PDGFRA oncogenic activation. Although first-line imatinib achieves remarkable prolonged disease control, the benefit of subsequent lines of treatment is more modest. Novel therapeutic strategies focus on overcoming the heterogeneity of KIT or PDGFRA secondary mutations and providing more potent inhibition of specific challenging mutations. This article reviews the current understanding and treatment of GIST, with an emphasis on recent advances.

The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor