Abstract

The collaboration between the DTB 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011078-11
Application #
9779787
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

O'Sullivan Coyne, Geraldine; Chen, Alice P; Meehan, Robert et al. (2017) PARP Inhibitors in Reproductive System Cancers: Current Use and Developments. Drugs 77:113-130
Reinhold, William C; Varma, Sudhir; Sunshine, Margot et al. (2017) The NCI-60 Methylome and Its Integration into CellMiner. Cancer Res 77:601-612
Cristofaro, J V; Ansher, S S; Zwiebel, J A et al. (2017) National Cancer Institute Formulary: A Public-Private Partnership Providing Investigators Access to Investigational Anticancer Agents. Clin Pharmacol Ther 101:616-618
Kummar, Shivaani; O'Sullivan Coyne, Geraldine; Do, Khanh T et al. (2017) Clinical Activity of the ?-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors (Aggressive Fibromatosis). J Clin Oncol 35:1561-1569
Ji, Jiuping; Zhang, Yiping; Redon, Christophe E et al. (2017) Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay. PLoS One 12:e0171582
Lin, Frank I; Gonzalez, E M; Kummar, S et al. (2017) Utility of (18)F-fluoroestradiol ((18)F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy. Eur J Nucl Med Mol Imaging 44:500-508
Lih, Chih-Jian; Harrington, Robin D; Sims, David J et al. (2017) Analytical Validation of the Next-Generation Sequencing Assay for a Nationwide Signal-Finding Clinical Trial: Molecular Analysis for Therapy Choice Clinical Trial. J Mol Diagn 19:313-327
Balasubramanian, Priya; Kinders, Robert J; Kummar, Shivaani et al. (2017) Antibody-independent capture of circulating tumor cells of non-epithelial origin with the ApoStream® system. PLoS One 12:e0175414
Holbeck, Susan L; Camalier, Richard; Crowell, James A et al. (2017) The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity. Cancer Res 77:3564-3576
Srivastava, Apurva K; Navas, Tony; Herrick, William G et al. (2017) Effective implementation of novel MET pharmacodynamic assays in translational studies. Ann Transl Med 5:3

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