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]
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
Please note that most posters on this site present work that is preliminary in nature and has not been peer reviewed.
This poster is open access subject to the CC BY-NC Creative Commons 3.0 License