Epigenetics: an alternative pathway in GISTs tumorigenesis

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors resistant to conventional therapies.
• While genetic mutations are studied, the role of reversible epigenetic changes in GISTs is underappreciated.
• Epigenetic malfunctions contribute to malignant transformation and altered cellular communication.

Purpose of the Study:

• To review the known epigenetic mechanisms involved in GIST pathogenesis, progression, and treatment resistance.
• To highlight the potential of targeting epigenetic alterations as a therapeutic strategy for GISTs.

Main Methods:

• Literature review of epigenetic mechanisms in GISTs.
• Analysis of DNA methylation, miRNA expression, and histone modifications in GIST development.
• Examination of GIST resistance to therapy in relation to epigenetic factors.

Main Results:

• Epigenetic alterations, including DNA hyper/hypomethylation and abnormal histone modification, play a significant role in GIST pathology.
• These epigenetic changes influence GIST treatment response, prognosis, and overall survival.
• Reversible epigenetic modifications are implicated in GIST onset, progression, and therapeutic resistance.

Conclusions:

• Epigenetic mechanisms are critical drivers in GIST development and resistance.
• Targeting reversible epigenetic changes, such as through inhibitors of histone acetyltransferase, deacetylase, and DNA methyltransferases, presents a novel therapeutic avenue for GIST treatment.
• Exploiting epigenetic alterations may help overcome GIST resistance and metastasis.