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SWI/SNF缺陷型恶性肿瘤:免疫肿瘤治疗的最佳候选对象?

SWI/SNF-deficient Malignancies: Optimal Candidates for Immune-oncological Therapy?

作者信息

Agaimy Abbas

机构信息

Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

出版信息

Adv Anat Pathol. 2023 May 1;30(3):211-217. doi: 10.1097/PAP.0000000000000366. Epub 2022 Sep 5.

Abstract

Inactivation of different subunits of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex has emerged as one of the most frequent genetic pathways driving a variety of neoplasms of diverse histogenesis, originating in different organs. With few exceptions, most SWI/SNF-deficient malignancies pursue a highly aggressive clinical course resulting in widespread disease dissemination either at or soon after diagnosis, ultimately causing patients' death soon after diagnosis, despite the apparently curative treatment intention. To date, no satisfactorily effective systemic chemotherapy has been established for treating these diseases. This disappointing finding underlines the urgent need for an effective systemic therapy that would enable sufficient intermediate to long-term disease control. Recently, SWI/SNF-deficiency has increasingly emerged as pivotal in cancer immunogenicity and hence a promising biomarker predicting response to immune-checkpoint inhibition therapy utilizing several recently established drugs. This review summarizes the most recent literature on this topic with emphasis on the entities that most likely represent suitable candidates for immune therapy.

摘要

开关/蔗糖非发酵(SWI/SNF)染色质重塑复合物不同亚基的失活已成为驱动多种不同组织发生、起源于不同器官的肿瘤的最常见遗传途径之一。除少数例外,大多数SWI/SNF缺陷型恶性肿瘤的临床病程高度侵袭性,导致在诊断时或诊断后不久疾病广泛播散,尽管有明显的治愈性治疗意图,但最终仍导致患者在诊断后不久死亡。迄今为止,尚未建立令人满意的有效全身化疗方案来治疗这些疾病。这一令人失望的发现凸显了迫切需要一种有效的全身治疗方法,以实现足够的中长期疾病控制。最近,SWI/SNF缺陷在癌症免疫原性中越来越重要,因此成为一种有前景的生物标志物,可预测使用几种最近获批药物的免疫检查点抑制疗法的反应。本综述总结了关于该主题的最新文献,重点关注最有可能成为免疫治疗合适候选者的实体。

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