Abstract IA012: Generation and Mining of a Pediatric-focused Cancer Cell Line Atlas to Define Druggable Genetic Interactions in Childhood Malignancies

IF 5.3 2区医学 Q1 ONCOLOGY

Molecular Cancer Therapeutics Pub Date : 2024-06-10 DOI:10.1158/1538-8514.synthleth24-ia012

Ron Firestein

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引用次数: 0

Abstract

Pediatric solid and central nervous system tumors are the primary cause of cancer-related fatalities in children. Discovering novel targeted therapies requires utilizing pediatric cancer models that accurately mirror the patient's illness. However, the creation and evaluation of these models have significantly trailed adult cancer research, emphasizing the pressing demand for pediatric-centric cell line repositories. Here, we establish a centralized collection of over 450 childhood cancer cell lines. We subjected over 250 of these cell lines to comprehensive multi-omics analyses (including DNA sequencing, RNA sequencing, and DNA methylation analysis), while concurrently conducting pharmacological screenings and genetic CRISPR-Cas9 loss-of-function assays to unveil pediatric-specific treatment avenues and biomarkers. Machine learning approaches were then applied to uncover genotype-phenotype relationships and synthetic lethal interactions. Our endeavor sheds light on the specific vulnerabilities of pathways in molecularly characterized pediatric tumor subclasses and reveals clinically relevant therapeutic opportunities linked with biomarkers. We offer access to the cell line data and resources through an open-access portal. Citation Format: Ron Firestein. Generation and Mining of a Pediatric-focused Cancer Cell Line Atlas to Define Druggable Genetic Interactions in Childhood Malignancies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA012.

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摘要 IA012：生成和挖掘以儿科为重点的癌症细胞系图谱，以确定儿童恶性肿瘤中可药用的基因相互作用

小儿实体瘤和中枢神经系统肿瘤是导致儿童因癌症死亡的主要原因。发现新型靶向疗法需要利用能准确反映患者病情的儿科癌症模型。然而，这些模型的创建和评估远远落后于成人癌症研究，这就强调了对以儿科为中心的细胞系库的迫切需求。在这里，我们建立了一个集中收集 450 多种儿童癌症细胞系的中心。我们对其中 250 多个细胞系进行了全面的多组学分析（包括 DNA 测序、RNA 测序和 DNA 甲基化分析），同时进行了药理学筛选和基因 CRISPR-Cas9 功能缺失检测，以揭示儿科特异性治疗途径和生物标志物。然后应用机器学习方法揭示基因型-表型关系和合成致死相互作用。我们的研究揭示了儿科肿瘤亚类分子特征通路的特定脆弱性，并揭示了与生物标志物相关的临床治疗机会。我们通过开放式门户网站提供细胞系数据和资源。引用格式：罗恩-弗雷斯坦生成和挖掘以儿科为重点的癌症细胞系图谱，以确定儿童恶性肿瘤中可用药的基因相互作用[摘要]。In：AACR 癌症研究特别会议论文集：扩展和转化癌症合成脆弱性；2024 年 6 月 10-13 日；加拿大魁北克省蒙特利尔。费城（宾夕法尼亚州）：AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA012.

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来源期刊

Molecular Cancer Therapeutics 医学-肿瘤学

CiteScore

11.20

自引率

1.80%

发文量

331

审稿时长

3 months

期刊介绍： Molecular Cancer Therapeutics will focus on basic research that has implications for cancer therapeutics in the following areas: Experimental Cancer Therapeutics, Identification of Molecular Targets, Targets for Chemoprevention, New Models, Cancer Chemistry and Drug Discovery, Molecular and Cellular Pharmacology, Molecular Classification of Tumors, and Bioinformatics and Computational Molecular Biology. The journal provides a publication forum for these emerging disciplines that is focused specifically on cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.