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 #
1ZIABC011078-06
Application #
8763337
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$379,135
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Murai, Junko; Zhang, Yiping; Morris, Joel et al. (2014) Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition. J Pharmacol Exp Ther 349:408-16
Jeong, Woondong; Park, Sook Ryun; Rapisarda, Annamaria et al. (2014) Weekly EZN-2208 (PEGylated SN-38) in combination with bevacizumab in patients with refractory solid tumors. Invest New Drugs 32:340-6
Jeong, Woondong; Rapisarda, Annamaria; Park, Sook Ryun et al. (2014) Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1*), in patients with refractory solid tumors. Cancer Chemother Pharmacol 73:343-8
Murai, Junko; Huang, Shar-Yin N; Renaud, Amelie et al. (2014) Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther 13:433-43
Jaspers, Janneke E; Kersbergen, Ariena; Boon, Ute et al. (2013) Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov 3:68-81
Kummar, Shivaani; Doroshow, James H (2013) Molecular targets in cancer therapy. Expert Rev Anticancer Ther 13:267-9
Park, Sook Ryun; Speranza, Giovanna; Piekarz, Richard et al. (2013) A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas. Cancer Chemother Pharmacol 71:981-90
Bhattacharyya, Sibaprasad; Kurdziel, Karen; Wei, Ling et al. (2013) Zirconium-89 labeled panitumumab: a potential immuno-PET probe for HER1-expressing carcinomas. Nucl Med Biol 40:451-7
Kummar, Shivaani; Anderson, Larry; Hill, Kimberly et al. (2013) First-in-human phase 0 trial of oral 5-iodo-2-pyrimidinone-2'-deoxyribose in patients with advanced malignancies. Clin Cancer Res 19:1852-7
Park, Sook Ryun; Davis, Myrtle; Doroshow, James H et al. (2013) Safety and feasibility of targeted agent combinations in solid tumours. Nat Rev Clin Oncol 10:154-68

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