Gastrointestinal stromal tumors: what do we know now?

Area of Science:

• Gastroenterology
• Oncology
• Pathology

Background:

• Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the GI tract.
• They originate from interstitial cells of Cajal and exhibit diverse morphologies, consistently expressing KIT (CD117) and/or DOG1.
• While often localized, GISTs have a significant recurrence and metastasis potential.

Purpose of the Study:

• To summarize the key aspects of GISTs, including their origin, diagnostic markers, clinical behavior, and molecular drivers.
• To highlight the role of tyrosine kinase inhibitors (TKIs) in managing unresectable GISTs and the challenge of drug resistance.
• To emphasize the importance of pathological assessment and routine genotyping for optimal GIST management and prognosis.

Main Methods:

• Review of current literature on GIST pathogenesis, diagnosis, and treatment.
• Analysis of molecular drivers, including KIT, PDGFRA, and wild-type mutations.
• Discussion of therapeutic strategies involving TKIs and the implications of drug resistance.

Main Results:

• GISTs are primarily driven by KIT (75%) or PDGFRA (10%) mutations, with ~15% being wild-type.
• TKIs like imatinib are effective but often face secondary mutation-induced resistance.
• Wild-type GISTs harbor diverse oncogenic drivers, necessitating comprehensive molecular profiling.

Conclusions:

• Accurate pathological assessment and routine genotyping are crucial for tailoring TKI therapy and predicting prognosis in GIST patients.
• Understanding the specific mutation profile is essential for selecting the appropriate TKI and managing potential drug resistance.
• Continued research into wild-type GIST drivers is vital for improving treatment strategies.