Ovarian Cancer Drug Olaparib Extends Progression Free Survival
A Phase II trial showed that Olaparib significantly extends progression-free survival of participants with SOC who had completed chemotherapy.
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Since: Dec 05
#1 May 23, 2011
Can PARP Inhibitors be tested with the Functional Profiling Platform?
Functional analysis of PARP inhibitors Olaparib (AZD-2281) and Iniparib (BSI-201) in human tumor primary cultures will be reported at the 2011 ASCO meeting (Nagourney, R., et al Proceedings Amer Soc Clin Oncol. 2011). PARP inhibitors are easily studied and provide interesting signals in the tissues studied. They've also identified synergy with other classes of drugs.
Poly ADP ribose polymerase (PARP) is a nuclear enzyme associated with response to DNA damage. Following single strand DNA breaks, the enzyme attaches a backbone of ADP and ribose that serves to initiate DNA repair. Certain classes of chemotherapeutics, specifically alkylating agents, can induce injury that results in extensive poly ADP ribosylation resulting in the exhaustion of intercellular pools of NAD and ATP ultimately leading to cell death.
Although PARP inhibitors have recently entered the clinical cancer literature mostly relating to the treatment of BRCA+ and triple negative patients, neither PARP nor PARP inhibitors are new to the cancer researcher community. Dr. Robert Nagourney first became interested following a 1988 study by Distelhorst from Case Western Reserve that described a mechanism of cell death that correlated with his work in childhood leukemia.
Nagourney's group has studied small molecule inhibitors of PARP for many years, and more recently, expanded these investigations to include Olaparib and Iniparib. They have explored the biology of PARP inhibitors, alone and in combination, in actual human tumor primary culture microspheroids (microclusters) in breast, ovarian and other cancers. The functional analysis platform explores the biology (real time) how PARP inhibitors enhance the effects of drugs and drug combinations before they are put into the patient.
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