Work Plan

CHEMORES is a so called Integrated Project where the work of groups conducting large clinical trials will be integrated with results from preclinical research groups. The consortium will undertake a multidisciplinary approach towards broadening the knowledge base on the molecular mechanisms underlying chemotherapy resistance, therapeutic escape, efficacy and toxicity. The achievement of this goal requires the integration of several scientific and technological activities. For the generation of clinically derived candidate resistance mechanisms excellent series of clinical samples are required as well as state-of-the-art platforms for genomics, proteomics and bioinformatics/biostatistics. For generation of additional innovative hypotheses on molecular chemotherapy resistance mechanisms the participation of leading basic research groups is essential. All these resources will be used also in subsequent functional and clinical validation of resistance mechanisms. The validated molecular mechanisms will be used to develop new predictive markers of chemotherapy response as well as to identify and initiate preclinical development of potential novel modulators of drug resistance.

Candidate mechanisms of drug resistance and therapeutic efficacy will be identified using genomic and proteomic analyses of sequential tumour samples and paired sera obtained before and after chemotherapy as well as experimental systems, including in vitro studies of tumour cell lines, transplanted human tumours and novel animal tumour models. These putative mechanisms will then be validated in further analyses of larger sets of tumour biopsies from patients. Functional studies of novel mechanisms and pathways will be also performed using the in vitro systems and animal models. The result of these activities will thus be a set of clinically and functionally validated mechanisms of chemotherapy resistance and therapeutic efficacy. The new information obtained in the project will be disseminated to the medical profession and other key stake holders, such as health care providers, patient organisations and policy makers.

Work Plan Overview

Page updated by Chemores June 1, 2007
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