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Background <p>The treatment of gastrointestinal stromal tumors (GIST) has evolved from a&#xa0;sequential administration of tyrosine kinase inhibitors (TKI) to a&#xa0;highly personalized mutation-driven strategy.</p> Objective <p>Presentation of the current developments in molecular diagnostics and targeted therapy for GIST, with a&#xa0;focus on new agents, their positioning in treatment lines and the management of rare molecular subtypes.</p> Material and methods <p>A&#xa0;selective literature review and analysis of current international and national guidelines (European Society for Medical Oncology ESMO, National Comprehensive Cancer Network NCCN, Onkopedia) and pivotal clinical trials (e.g., NAVIGATOR, INTRIGUE, CaboGIST, PEAK) were performed.</p> Results <p>Molecular genetic testing has become the standard of care before initiation of treatment and in cases of progression. The TKI imatinib remains the standard first-line treatment for most GIST mutations. Avapritinib is approved for the first-line treatment of GIST with platelet-derived growth factor receptor alpha (<i>PDGFRA</i>)D842V mutations and fills an important therapeutic gap. In the second-line setting ripretinib demonstrates efficacy comparable to sunitinib but with a&#xa0;more favorable safety profile and is established as a&#xa0;fourth-line therapy. For rare subtypes highly effective targeted therapies, some with tumor-agnostic approval, are available. The liquid biopsy is gaining clinical importance for the noninvasive detection of resistance mechanisms.</p> Conclusion <p>Modern treatment of GIST requires a precise molecular stratification at initial diagnosis and at each progression. Interdisciplinary molecular tumor boards are essential to identify the optimal evidence-based treatment for each patient and to further improve the prognosis.</p>

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Update zu molekularen Subtypen und zielgerichteten Therapien bei gastrointestinalen Stromatumoren

  • 期刊论文

  • 发表日期：

    2025年11月24日

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  • Aayushi Srivastava,
  • Jörg Trojan

摘要

Background

The treatment of gastrointestinal stromal tumors (GIST) has evolved from a sequential administration of tyrosine kinase inhibitors (TKI) to a highly personalized mutation-driven strategy.

Objective

Presentation of the current developments in molecular diagnostics and targeted therapy for GIST, with a focus on new agents, their positioning in treatment lines and the management of rare molecular subtypes.

Material and methods

A selective literature review and analysis of current international and national guidelines (European Society for Medical Oncology ESMO, National Comprehensive Cancer Network NCCN, Onkopedia) and pivotal clinical trials (e.g., NAVIGATOR, INTRIGUE, CaboGIST, PEAK) were performed.

Results

Molecular genetic testing has become the standard of care before initiation of treatment and in cases of progression. The TKI imatinib remains the standard first-line treatment for most GIST mutations. Avapritinib is approved for the first-line treatment of GIST with platelet-derived growth factor receptor alpha (PDGFRA)D842V mutations and fills an important therapeutic gap. In the second-line setting ripretinib demonstrates efficacy comparable to sunitinib but with a more favorable safety profile and is established as a fourth-line therapy. For rare subtypes highly effective targeted therapies, some with tumor-agnostic approval, are available. The liquid biopsy is gaining clinical importance for the noninvasive detection of resistance mechanisms.

Conclusion

Modern treatment of GIST requires a precise molecular stratification at initial diagnosis and at each progression. Interdisciplinary molecular tumor boards are essential to identify the optimal evidence-based treatment for each patient and to further improve the prognosis.