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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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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
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