Abstract

Our studies in the CS Project continue our identification of genetic determinants of chemotherapeutic sensitivity of agents that target CRC and ALL. In the ALL Project we obtain primary malignant cells for determining in vitro drug sensitivity and identifying genes associated with drug resistance in primary cancer tissue (46). This is not practical . for CRC. Our second approach for the CS project is to test for inherited determinants of drug sensitivity using LCLs derived from CEPH families. Three-generation pedigrees provide the power to evaluate the genetic contribution to anticancer drug cytotoxicity (41). Drugs that are relevant to the objectives of PAAR include: etoposide (ALL, CRC, CYP3A); vincristine and daunbrubicin (ALL, CYP3A); mercaptopurine and cytarabine (ALL); SN-38 and platinating agents (CRC). Complementary studies are being performed in CREATE (42) and we are working together to share baseline microarray data, genotyping on CEPH cell lines and statistical expertise (see letter from Dr. McLeod). We hypothesize that a significant component of cellular susceptibility to cytotoxic agents is due to heritable factors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01GM061393-08
Application #
7551142
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
8
Fiscal Year
2007
Total Cost
$237,667
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Zhou, Shuqin; Skaar, Debra J; Jacobson, Pamala A et al. (2018) Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit. Front Pharmacol 9:1436
House, Larry; Seminerio, Michael J; Mirkov, Snezana et al. (2018) Metabolism of megestrol acetate in vitro and the role of oxidative metabolites. Xenobiotica 48:973-983
Gamazon, Eric R; Trendowski, Matthew R; Wen, Yujia et al. (2018) Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma. Sci Rep 8:733
Li, M; Seiser, E L; Baldwin, R M et al. (2018) ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia. Pharmacogenomics J 18:35-42
Geeleher, Paul; Nath, Aritro; Wang, Fan et al. (2018) Cancer expression quantitative trait loci (eQTLs) can be determined from heterogeneous tumor gene expression data by modeling variation in tumor purity. Genome Biol 19:130
Wing, Claudia; Komatsu, Masaaki; Delaney, Shannon M et al. (2017) Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy. Stem Cell Res 22:79-88
Rudin, Shoshana; Marable, Marcus; Huang, R Stephanie (2017) The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment. Genomics Proteomics Bioinformatics 15:82-93
Geeleher, Paul; Huang, R Stephanie (2017) Exploring the Link between the Germline and Somatic Genome in Cancer. Cancer Discov 7:354-355
Geeleher, Paul; Zhang, Zhenyu; Wang, Fan et al. (2017) Discovering novel pharmacogenomic biomarkers by imputing drug response in cancer patients from large genomics studies. Genome Res 27:1743-1751
Eadon, Michael T; Hause, Ronald J; Stark, Amy L et al. (2017) Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach. Int J Mol Sci 18:

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