posted on 2024-10-30, 15:00authored byYasuhiro 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
Comparison of gene expression of CU-ACC cell lines and original PDXs. A, Overall correlation between gene expression in the cancer cell lines evaluated at the NCI and CU and their corresponding PDXs. Areas shaded in gray highlight the grouping of corresponding ACC cell lines and PDXs. B, Examples of coherent genes. Univariate analysis scatterplot of ABCB1 (MDR1) transcriptional expression level vs. ABCG2 (BCRP) and CYP21A2 transcriptional expression level vs. CYP11B1 transcriptional expression level. C, Example of differentially expressed genes related to cellular proliferation for the CU-ACC1 and CU-ACC2 cell lines and corresponding PDXs.
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ARTICLE 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.
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.