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具有横纹肌样特征的肿瘤中的 SWI/SNF 复合物改变:新型治疗方法及过继性细胞治疗的机会

英文原题:SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

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SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

PubMed 2023/07/06(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

SWI/SNF染色质重塑复合物是癌症中最显著改变的表观遗传调控因子之一。近年来,编码SWI/SNF相关蛋白的基因中的致病性突变已在许多实体瘤中被描述,包括具有横纹肌样特征的罕见且侵袭性恶性肿瘤,这些肿瘤在晚期或转移性情况下没有标准疗法。近年来,旨在恢复其功能的靶向药物临床试验结果令人沮丧。然而,临床前数据发现这些表观遗传改变与免疫治疗反应之间存在关联。因此,在SWI/SNF复合物改变相关肿瘤中采用免疫治疗策略的理由是充分的。在此,我们综述SWI/SNF复合物及其功能障碍如何驱动横纹肌样肿瘤的发生,以及提出的逆转这一改变的策略和有前景的新型治疗方法,包括免疫检查点抑制和过继细胞疗法。

展开英文摘要原文

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results.

However, preclinical data have found an association between these epigenetic alterations and response to immune therapy.

Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong.

Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy.

论文信息

作者
Soto-Castillo JJ、Llavata-Marti L、Fort-Culillas R、Andreu-Cobo P、Moreno R、Codony C、García Del Muro X、Alemany R
单位
Medical Oncology Department, Catalan Institute of Oncology (ICO), 08908 Hospitalet de Llobregat, Spain.Spain
文献类型
综述
期刊
International journal of molecular sciences2023 Jul 6
原文标识
PubMed 37446319 · DOI 10.3390/ijms241311143