Regrowth Concentration Zero (RC0) as Complementary Endpoint Parameter to Evaluate Compound Candidates During Preclinical Drug Development for Cancer Treatment
- *Corresponding Author:
- Dr. Yakisich J. Sebastian
Department of Clinical Neuroscience
Huddinge Division of Neurology, Karolinska Institute
Huddinge University Hospital
Sweden Hospital, S-141 86, Huddinge
Tel: +46 8 585 89 533
Fax: +46 8 585 83810
E-mail: [email protected]
Received Date: November 01, 2009; Accepted Date: November 25, 2009; Published Date: November 25, 2009
Citation: Avramidis D, Cruz M, Sidén Å, Tasat DR, Yakisich JS (2009) Regrowth Concentration Zero (RC0) as Complementary Endpoint Parameter to Evaluate Compound Candidates During Preclinical Drug Development for Cancer Treatment. J Cancer Sci Ther 1: 019-024. doi:10.4172/1948-5956.1000003
Copyright: © 2009 Avramidis D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The screening process for potential anticancer drugs involves expensive and time consuming preclinical and clinical trials (CT) before a drug is approved for clinical use (CU). At present, there is a “bottleneck” at the CT/CU transition because many drugs that showed promising results during preclinical research did not pass clinical trials. We speculated that the endpoint parameters (the inhibitory concentration 50 (IC50) or lethal concentration 100 (CL100)) commonly used in proliferation assays for short-term periods (24-72 h) are not useful to predict the antiproliferative effect in vivo, especially during clinical trials. We propose the use of a parameter, regrowth concentration 0 (RC0), which will define the concentration and time necessary to kill 100 % of the cells and prevent regrowth when drug is removed. The RC0 might introduce a new bottleneck at the preclinical stage, “preclinical bottleneck”, that will select for drugs with more chances to pass clinical trials and improve the success rate of anticancer screening programs. Our proposal is supported by experiments done with the DBTRG-05MG human glioma cell lines exposed to short and long-term incubation with three different DNA replication inhibitors (aphidicolin, hydroxyurea and etoposide) and retrospective analysis of clinical trials for these drugs.