Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
The Royal Marsden NHS Foundation Trust, London, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.
Int J Biochem Cell Biol. 2023 Apr;157:106383. doi: 10.1016/j.biocel.2023.106383. Epub 2023 Feb 1.
Desmoplastic small round cell tumour (DSRCT) is an ultra-rare soft tissue sarcoma that is characterised by aggressive disease and dismal patient outcomes. Despite multi-modal therapy, prognosis remains poor and there are currently no effective targeted therapies available for patients with this disease. Advances in comprehensive molecular profiling approaches including next generation sequencing and proteomics hold the promise of identifying new therapeutic targets and biomarkers. In this review, we provide an overview of the current status of molecular profiling studies in DSRCT patient specimens and cell lines, highlighting the key genomic, epigenetic and proteomic findings that have contributed to our biological knowledge base of this recalcitrant disease. In-depth analysis of these molecular profiles has led to the identification of promising novel and repurposed candidate therapies that are suitable for translation into clinical trials. We further provide a perspective on how future integrated studies including proteogenomics could further enrich our understanding of this ultra-rare entity and deliver progress that will ultimately impact the outcomes of patients with DSRCT.
促结缔组织增生性小圆细胞肿瘤（DSRCT）是一种极为罕见的软组织肉瘤，其疾病侵袭性强，患者预后较差。尽管采用多模式治疗，预后仍然较差，目前尚无针对这种疾病的有效靶向治疗方法。包括下一代测序和蛋白质组学在内的综合分子分析方法的进步有望确定新的治疗靶点和生物标志物。在这篇综述中，我们概述了 DSRCT 患者标本和细胞系中分子分析研究的现状，重点介绍了有助于我们对这种难治性疾病的生物学知识库的关键基因组、表观基因组和蛋白质组学发现。对这些分子谱的深入分析导致确定了有前途的新型和再利用候选治疗方法，这些方法适合转化为临床试验。我们进一步提供了一个视角，即未来包括蛋白质基因组学在内的综合研究如何进一步丰富我们对这种超罕见实体的理解，并取得最终影响 DSRCT 患者治疗结果的进展。
