Background: No predictive biomarkers have been identified for VEGFR- and mTOR-inhibitors treatments, the 2 standards of care in mRCC. The PREDICT project (Personalised RNA Interference to Enhance the Delivery of Individualised Cytotoxic and Targeted Therapeutics) is a EU-funded research program built on the Consortium of Academic Centers, Universities, Research Institutions, SME & industrial members. Two biomarker discovery clinical trials using Everolimus (E-PREDICT) and Sunitinib (S-PREDICT) treatment in patients with mRCC have been developped and are recruiting.The 3 cornerstones of the PREDICT approach are: (i) to acquire paired pre-treatment biopsies and on-treatment nephrectomy (NE) specimens for molecular analyses and integration with clinical efficacy data; (ii) to identify genes regulating drug resistance in ex vivo RCC cultures from trial patients by a novel personalized functional genomics screening approach; (iii) to integrate functional data with genome wide molecular analyses of pre- and on-treatment samples in order to identify clinically relevant mechanisms of drug resistance and the next generation of predictive biomarkers. Methods: International multicentre single arm phase II trials of EV or SU administered peri-NE in patients with untreated mRCC are ongoing. Fresh tissue is collected in a quality-controlled setting by core biopsy of primary tumours before treatment. Treatment (EV or SU) is administered for a 2 cycle period of time (EV: 10 mg/d po for 6 wks; SU: 2 cycles of 50 mg/d po for 4 wks followed by 2 wks off drug) followed by NE. On NE specimen, fresh tissue is collected with similar standardized tissue collection and processing protocols for both genomic analysis and ex-vivo expansion in order to develop RCC cell culture from any NE as well as mice-xenografts. Ex vivo cultures from NE specimens will be used for personalized functional genomic RNA interference screening. Patient resumes treatment after wound is healed until progression. Functional imaging (perfusion CT) as clinical data are collected. The primary clinical endpoint is the safety of peri-NE E/S. Secondary endpoints include efficacy and biomarker measurements. Sample size: 60 pts in both biomarker discovery and validation cohorts per trial will allow the identification and validation of several potential predictive biomarkers per drug with an expected AUC of >0.8 while controlling the false positive rate < 5%. Results: To date 33 patients have been enrolled in the S- PREDICT Trial. Preliminary analysis of 25 first paired pre- treatment biopsies and frozen nephrectomy specimen provided sufficient and quality controlled material for genomic analysis. Three RCC cultures have been tested for functional genomic RNA interference screening. Planned genomic analyses and functional genomic screens will be further discussed.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1746. doi:1538-7445.AM2012-1746