Pharmacokinetics & Drug Delivery | Cancer Therapeutics | Molecular Pharmacology | Pediatric Oncology | Oncology Agents
Molecular determinants of T-cell acute lymphoblastic leukaemia sensitivity to the pre-prodrug PR-104
Donya Moradi Manesh*, Barbara Szymanska, Hernan Carol, Ingrid Boehm, Kathryn Evans, Stephen Jamieson, William R Wilson, Peter J Houghton, Malcolm A Smith, Richard B Lock
*Corresponding author: Donya Moradi Manesh
Leukaemia Biology Program, Children's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, NSW, Australia
F1000Posters 2012, 3: 203 (poster) [English]
Poster [1.66 MB]
Presented at
24th Lorne Cancer Conference 2012,
8 - 10 Feb 2012, 259
PR-104 is a pre-prodrug hydrolysed rapidly in vivo to PR-104A, which is activated by one-electron reductases under hypoxia to DNA crosslinking mustard metabolites. PR-104A is also activated under aerobic conditions by aldo-keto reductase 1C3 (AKR1C3).
Our findings indicate that AKR1C3 expression is an important determinant of in vitro and in vivo sensitivity to PR-104/PR-104A, and have implications for the clinical development of PR-104 since patients with T-acute lymphoblastic leukemia may represent a particularly responsive population.
No relevant competing interests disclosed.
The National Cancer Institute USA, NOI-CM-91001-03
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