The collaboration between the LMP and DCTD has been responsible for the development of several new pharmacodynamic assays, including an ultrasensitive immunofluorescence assay for gamma H2AX (DNA double strand break detector) in tumor tissue biopsies, and ELISAs for topoisomerase I and poly ADP-ribose polymerase (PARP). These assays have been essential for first in human clinical trials of PARP inhibitors in combination with topoisomerase I inhibitors as well as of novel, non-camptothecin topoismerase I inhibitors that have been activated in the NIH Clinical Center. In addition, collaborations with the Medical Oncology Branch have facilitated the development of the new DNA methyltransferase inhibitor fluorodeoxycytidine used in combination with tetrahydrouridine, drugs that have been produced by DCTD for study by the CCR. Additional collaborations have developed around our use of the NCI 60 for systems pharmacology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011078-05
Application #
8552970
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$392,941
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Jensen, Niels Frank; Agama, Keli; Roy, Amit et al. (2016) Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations. J Exp Clin Cancer Res 35:56
Parchment, Ralph E; Doroshow, James H (2016) Pharmacodynamic endpoints as clinical trial objectives to answer important questions in oncology drug development. Semin Oncol 43:514-25
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Krushkal, Julia; Zhao, Yingdong; Hose, Curtis et al. (2016) Concerted changes in transcriptional regulation of genes involved in DNA methylation, demethylation, and folate-mediated one-carbon metabolism pathways in the NCI-60 cancer cell line panel in response to cancer drug treatment. Clin Epigenetics 8:73
Kummar, Shivaani; Wade, James L; Oza, Amit M et al. (2016) Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer. Invest New Drugs 34:355-63
Do, Khanh; Cao, Liang; Kang, Zhigang et al. (2015) A Phase II Study of Sorafenib Combined With Cetuximab in EGFR-Expressing, KRAS-Mutated Metastatic Colorectal Cancer. Clin Colorectal Cancer 14:154-61

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