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A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma Cell Lines, PDX, and Patient
Yasuhiro Arakawa1, Fathi Elloumi1, Sudhir Varma1
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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.
Insights
A new database, ACC_CellMinerCDB, aids precision medicine for adrenocortical carcinoma (ACC). It links genomic data from cell lines and patient samples to drug responses, identifying potential new therapies.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Adrenocortical carcinoma (ACC) is a rare, heterogeneous cancer with poor prognosis.
- Challenges in ACC diagnosis and treatment necessitate precision medicine approaches.
- Comprehensive genomic resources and experimental models are crucial for personalized ACC therapies.
Purpose of the Study:
- To present ACC_CellMinerCDB, a novel database integrating genomic and drug sensitivity data for ACC.
- To validate ACC cell lines as research models by comparing them to surgical samples.
- To identify potential therapeutic targets and drug repurposing opportunities for ACC.
Main Methods:
- Compiled a database (ACC_CellMinerCDB) with genomic data from ACC cell lines, patient-derived xenografts, and surgical samples.
- Integrated drug sensitivity data for over 2,400 drugs from NCI and NCATS.
- Analyzed shared genomic pathways and treatment markers (e.g., MDR-1, SLFN11) between cell lines and patient samples.
Main Results:
- ACC_CellMinerCDB demonstrates shared genomic pathways between ACC cell lines and surgical samples, validating cell line utility.
- Identified key treatment markers relevant to ACC.
- Revealed potential for repurposing drugs, such as temozolomide, for ACC treatment.
Conclusions:
- ACC_CellMinerCDB serves as a foundational resource for preclinical ACC research.
- The database facilitates the exploration of personalized therapeutic strategies for adrenocortical carcinoma.
- This resource supports the advancement of precision medicine in ACC by linking genomic insights to drug responses.
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