EORTC European Union funded projects
CHEMORES “Molecular mechanisms underlying chemotherapy resistance, therapeutic escape, efficiency and toxicity”
Project start date: 1st Feb. 2007
Project duration: 60 months
Project website: www.chemores.org
The overall aim of the proposed Integrated Project is to improve the outcome of cancer chemotherapy by developing novel tools to predict tumor response to treatment as well as individual toxicity to chemotherapy. The project will seek to identify and validate mechanisms of intrinsic and acquired chemotherapy resistance, as well as predictors of efficacy and of individual toxicity. This is achieved by integrating the work of groups conducting large clinical trials with preclinical research groups, as well as with state of the art-platforms for genomic and proteomic analyses and bioinformatics. The participants have chosen to focus on melanoma and lung cancer as model tumors of separate histogenetic types exhibiting intrinsic resistance and/or a high degree of acquired resistance to chemotherapy.
Candidate mechanisms of drug resistance and therapeutic efficacy will be identified using genomic and proteomic analyses of sequential tumor samples and paired sera obtained before and after chemotherapy as well as experimental systems, including in vitro studies of tumor cell lines, transplanted human tumors and novel animal tumor models,. These putative mechanisms will then be validated in further analyses of larger sets of tumor biopsies from patients. Functional studies of novel mechanisms and pathways will be also performed using 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. Likewise, large scale genomic analyses of patients receiving chemotherapy as part of clinical trials will be performed in order to validate novel markers of individual toxicity following chemotherapy.
The novel knowledge obtained through the project will lead to new tools for prediction of treatment outcome as well as toxicity of chemotherapy. This knowledge may also be used to identify and prepare for preclinical development of potential novel modulators of drug resistance based on validated mechanisms and pathways. The new information obtained in the Integrated Project will be disseminated to the medical profession and other key stake holders, such as health care providers, patient organisations and policy makers.