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Role of the SWI/SNF complex in the development of digestive tumors (Review)
Shihang Xue1, Haiting Yu1, Liuhai Zeng1
1Department of General Surgery, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo Fourth Hospital, Ningbo, Zhejiang 315700, P.R. China.
Abstract:
The ATP‑dependent switch/sucrose non-fermentable (SWI/SNF) complex serves a crucial role in systematically modifying chromatin structure and regulating cellular epigenetics. A decreased expression or mutations in the SWI/SNF complex can lead to a series of physiological and pathological changes. Several gene sequencing studies have identified diverse mutations in the SWI/SNF subunits across gastrointestinal cancers. Tumor cells with these mutations are dedifferentiated and more aggressive, with early metastases, including to lymph nodes, often associated with poor prognosis. At present, for tumors with SWI/SNF mutations, the main treatment regimen is based on the phenomenon of synthetic lethality. The present review explores the common mutational mechanisms that affect these subunits and their impact on gastrointestinal tumors, as well as the emerging therapeutic approaches, thereby providing a substantive foundation for further clinical research in this field.
Insights
Mutations in the ATP-dependent switch/sucrose non-fermentable (SWI/SNF) complex are common in gastrointestinal cancers, driving aggressive tumors. Synthetic lethality offers a promising therapeutic strategy for these SWI/SNF-mutated cancers.
Area of Science:
- Epigenetics and Chromatin Biology
- Cancer Genomics
- Gastrointestinal Oncology
Background:
- The ATP-dependent switch/sucrose non-fermentable (SWI/SNF) complex is vital for chromatin remodeling and epigenetic regulation.
- Altered SWI/SNF complex expression or mutations are linked to various physiological and pathological conditions.
- SWI/SNF subunit mutations are frequently identified in gastrointestinal cancers, correlating with dedifferentiation and aggressive phenotypes.
Purpose of the Study:
- To review common SWI/SNF gene mutations in gastrointestinal tumors.
- To explore the impact of these mutations on tumor behavior and prognosis.
- To discuss emerging therapeutic strategies, particularly synthetic lethality, for SWI/SNF-mutated cancers.
Main Methods:
- Literature review of gene sequencing studies in gastrointestinal cancers.
- Analysis of the functional consequences of SWI/SNF mutations.
- Examination of current and novel therapeutic approaches targeting SWI/SNF-mutated tumors.
Main Results:
- SWI/SNF mutations are associated with dedifferentiated, aggressive tumor cells and poor prognosis in gastrointestinal cancers.
- These mutations often lead to early metastasis, including lymph node involvement.
- Synthetic lethality is the primary treatment paradigm for SWI/SNF-mutated tumors.
Conclusions:
- Understanding SWI/SNF mutational mechanisms is crucial for gastrointestinal cancer treatment.
- Emerging therapies targeting synthetic lethality hold promise for improving outcomes.
- This review provides a foundation for future clinical research in SWI/SNF-mutated gastrointestinal malignancies.
