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

Author:

Arakawa Yasuhiro1ORCID,Elloumi Fathi1ORCID,Varma Sudhir1ORCID,Khandagale Prashant1ORCID,Jo Ukhyun1ORCID,Kumar Suresh1ORCID,Roper Nitin1ORCID,Reinhold William C.1ORCID,Robey Robert W.2ORCID,Takebe Naoko1ORCID,Gottesman Michael M.2ORCID,Thomas Craig J.3ORCID,Boeva Valentina4ORCID,Berruti Alfredo5ORCID,Abate Andrea6ORCID,Tamburello Mariangela6ORCID,Sigala Sandra6ORCID,Hantel Constanze78ORCID,Weigand Isabel9ORCID,Wierman Margaret E.10ORCID,Kiseljak-Vassiliades Katja10ORCID,Del Rivero Jaydira1ORCID,Pommier Yves1ORCID

Affiliation:

1. Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 1

2. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 3

3. National Institutes of Health, Rockville, Maryland. 4

4. Department of Computer Science, Institute for Machine Learning, ETH Zurich, Zurich, Switzerland. 5

5. Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology Unit, University of Brescia, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili, Brescia, Italy. 6

6. Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 7

7. Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, and University of Zurich, Zürich, Switzerland. 8

8. Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany. 9

9. Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany. 10

10. Department of Medicine-Endocrinology/Metabolism/Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, Colorado. 2

Abstract

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.

Publisher

American Association for Cancer Research (AACR)

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