tailieunhanh - Báo cáo y học: "Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer: rationale for patient selection and efficacy monitoring"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer: rationale for patient selection and efficacy monitoring. | Open Access Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer rationale for patient selection and efficacy monitoring Xi-De Wang Karen Reeves Feng R Luo Li-An Xu Francis Lee Edwin Clark and Fei Huang Address Pharmaceutical Research Institute Bristol-Myers Squibb Princeton New Jersey 08543 USA. Correspondence Xi-De Wang. Email Fei Huang. Email Published 29 November 2007 Genome Biology 2007 8 R255 doi gb-2007-8- 11-r255 The electronic version of this article is the complete one and can be found online at http 2007 8 ll R255 Received 15 June 2007 Revised 22 October 2007 Accepted 29 November 2007 2007 Wang et al. licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Dasatinib is a potent multi-targeted kinase inhibitor that was recently approved for treatment of chronic myelogenous leukemia resistant to imatinib. To aid the clinical development of dasatinib in prostate cancer we utilized preclinical models to identify potential molecular markers for patient stratification and efficacy monitoring. Results Using gene expression profiling we first identified 1 74 genes whose expression was highly correlated with in vitro sensitivity of 16 cell lines and thus considered as candidate efficacy predictive markers. Among these are important prostatic cell lineage markers cytokeratin 5 androgen receptor and prostate specific antigen. Our results indicate that basal type cell lines with high expression of cytokeratin 5 and low expression of androgen receptor or prostate specific antigen are sensitive to dasatinib. To identify markers as surrogates for biological activity we treated cell lines with dasatinib .