GDF15 as a Novel Biomarker for Monitoring Danusertib ActivityPatrizia Carpinelli1*, Paolo Cappella1, Marco Losa1,3, Valter Croci1, Roberta Bosotti1, Luisa Lanfrancone2, Antonella Isacchi1 and Jürgen Moll1
- *Corresponding Author:
- Patrizia Carpinelli
Nerviano Medical Sciences Srl, Viale Pasteur
10, 20014 Nerviano (MI) Italy
Tel: +39 0331 581532
E-mail: [email protected]
Received date: May 26, 2011; Accepted date: August 25, 2011; Published date: December 30, 2011
Citation: Carpinelli P, Cappella P, Losa M, Croci V, Bosotti R, et al. (2011) GDF15 as a Novel Biomarker for Monitoring Danusertib Activity. J Mol Biomark Diagn S2:001. doi:10.4172/2155-9929.S2-001
Copyright: © 2011 Carpinelli P, 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.
Biomarkers that indicate biological activity and/or efficacy are a potentially useful tool in the development of molecularly targeted therapeutics. Most pharmacodynamic assays measure the response to drugs in tissues, a procedure requiring tissue biopsies, which is often not available. In this study, we identify GDF15 as a potential plasma biomarker for Danusertib (formerly PHA-739358), an Aurora kinase inhibitor, currently in phase I/II clinical studies. Cell lysates and cell-free culture supernatants from human tumor isogenic cell lines were assessed for GDF15 levels following treatment with Danusertib, by using Western Blotting and Elisa. GDF15 levels were also measured in plasma from xenografted mice as well as in plasma from patients before and after Danusertib treatment. At the protein level an increased level of GDF15 was found in tissue culture cells after Danusertib treatment and GDF15 expression was also detected in plasma of xenografted mice treated with the compound. Hence, both cellular and xenograft models of human cancer showed a clear correlation with p53 pathway activation. Danusertib treatment also resulted in a significantly increased expression of GDF15 protein levels in the plasma of examined patients, underlining technical feasibility of translating this putative biomarker to clinical studies. Determination of GDF15 levels in plasma is feasible and enabled us to follow the kinetic of Danusertib activity in plasma from cancer xenografted mice and from patients. These findings should allow us to evaluate systematically the kinetics of p53 activation by Danusertib in future clinical studies.