A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma Cell Lines, PDX, and Patient Samples.

IF 2 Q3 ONCOLOGY Cancer research communications Pub Date : 2024-09-01 DOI:10.1158/2767-9764.CRC-24-0100
Yasuhiro Arakawa, Fathi Elloumi, Sudhir Varma, Prashant Khandagale, Ukhyun Jo, Suresh Kumar, Nitin Roper, William C Reinhold, Robert W Robey, Naoko Takebe, Michael M Gottesman, Craig J Thomas, Valentina Boeva, Alfredo Berruti, Andrea Abate, Mariangela Tamburello, Sandra Sigala, Constanze Hantel, Isabel Weigand, Margaret E Wierman, Katja Kiseljak-Vassiliades, Jaydira Del Rivero, Yves Pommier
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Abstract

Adrenocortical carcinoma (ACC) is a rare and highly heterogeneous disease with a notably poor prognosis due to significant challenges in diagnosis and treatment. Emphasizing on the importance of precision medicine, there is an increasing need for comprehensive genomic resources alongside well-developed experimental models to devise personalized therapeutic strategies. We present ACC_CellMinerCDB, a substantive genomic and drug sensitivity database (available at https://discover.nci.nih.gov/acc_cellminercdb) comprising ACC cell lines, patient-derived xenografts, surgical samples, and responses to more than 2,400 drugs examined by the NCI and National Center for Advancing Translational Sciences. This database exposes shared genomic pathways among ACC cell lines and surgical samples, thus authenticating the cell lines as research models. It also allows exploration of pertinent treatment markers such as MDR-1, SOAT1, MGMT, MMR, and SLFN11 and introduces the potential to repurpose agents like temozolomide for ACC therapy. ACC_CellMinerCDB provides the foundation for exploring larger preclinical ACC models.

Significance: ACC_CellMinerCDB, a comprehensive database of cell lines, patient-derived xenografts, surgical samples, and drug responses, reveals shared genomic pathways and treatment-relevant markers in ACC. This resource offers insights into potential therapeutic targets and the opportunity to repurpose existing drugs for ACC therapy.

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整合来自肾上腺皮质癌 (ACC) 细胞系、PDX 和患者样本的基因组和药理学数据的数据库工具。
肾上腺皮质癌(ACC)是一种罕见的高度异质性疾病,由于诊断和治疗方面的巨大挑战,其预后明显较差。在强调精准医疗重要性的同时,人们越来越需要全面的基因组资源以及完善的实验模型来设计个性化的治疗策略。我们介绍的ACC_CellMinerCDB是一个实质性的基因组和药物敏感性数据库(可在https://discover.nci.nih.gov/acc_cellminercdb),包括ACC细胞系、患者衍生的异种移植、手术样本以及对NCI和NCATS研究的2400多种药物的反应。该数据库揭示了 ACC 细胞系和手术样本之间共享的基因组通路,从而验证了细胞系作为研究模型的真实性。它还允许探索相关的治疗标记,如 MDR-1、SOAT1、MGMT、MMR 和 SLFN11,并介绍了将替莫唑胺等药物重新用于 ACC 治疗的可能性。ACC_CellMinerCDB 为探索更大的临床前 ACC 模型奠定了基础。
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