Targeting tumor dormancy: the next frontier in gastrointestinal stromal tumor therapy

Area of Science:

• Oncology
• Gastroenterology
• Molecular Biology

Background:

• Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, driven by KIT/PDGFRA mutations.
• Imatinib (IM) therapy represents a paradigm of precision medicine in GIST treatment.
• Acquired resistance to IM is a significant challenge, leading to poor prognosis in GIST patients.

Purpose of the Study:

• To explore novel mechanisms of imatinib resistance in GIST.
• To investigate the roles of tumor dormancy and cancer stem cell (CSC) biology in GIST.
• To propose innovative therapeutic strategies for overcoming IM resistance in GIST.

Main Methods:

• This review summarizes fundamental regulatory mechanisms of tumor dormancy and CSC biology.
• Candidate manifestations of these states in GIST are discussed.
• The review proposes therapeutic strategies based on insights into dormancy and CSCs.

Main Results:

• Tumor dormancy and CSC models are linked to therapy resistance, recurrence, and metastasis across malignancies.
• Emerging evidence suggests non-genetic persistence states, including dormant cells and KITlow stem-like/CSC-like subpopulations, exist in GIST.
• These states are critical for understanding and overcoming IM resistance.

Conclusions:

• Understanding tumor dormancy and CSC biology is crucial for improving GIST treatment outcomes.
• Targeting these non-genetic persistence states may offer novel therapeutic avenues.
• Innovative strategies are needed to overcome imatinib resistance and enhance patient prognosis in GIST.