Cancer represents one of the most serious health problems in Europe. It is estimated that the two diseases studied in the CHEMORES project, lung cancer and melanoma, alone caused over 350,000 deaths in Europe in 2002. The two main subtypes of lung cancer are small cell lung cancer (SCLC) which is highly chemosensitive with response rates of 80% to cisplatin and etoposide chemotherapy; and non-small cell lung cancer (NSCLC) that is moderately chemosensitive with response rates of 30-60%, depending on the stage of disease, to platinum in combination with gemcitabine, or vinorelbine or a taxane. In contrast, only a small minority of patients with melanoma respond to chemotherapy. There is no effective systemic therapy for metastatic melanoma.

The cancer problem is growing due to the increasing age of the population and the societal economic consequences of cancer are enormous. An important contributing factor in cancer mortality is the fact that the majority of the most common malignant diseases are refractory to systemic chemotherapy in the advanced stage. The overall aim of CHEMORES is to improve the outcome of cancer chemotherapy by developing novel tools to predict tumour response to treatment as well as individual toxicity to chemotherapy. We will seek to identify and validate mechanisms of intrinsic and acquired chemotherapy resistance, as well as predictors of efficacy and of individual toxicity. It is not our intention to develop new treatment modalities but rather to examine treatment failure in currently used chemotherapy regimens.

Cancer has a large negative effect on quality of life. This is related both to suffering and death from disease but also to severe side-effects of the given therapies. By addressing chemotherapy resistance we hope to improve the effects of therapy and increase the possibility to cure cancer patients. Even if complete cure is not achieved, better treatment effects may have palliative effects reducing the suffering. Also, a better selection of the patients given a certain therapy could reduce the negative side-effects associated with inefficient treatments. Previous attempts to develop predictive tests for resistance or sensitivity to chemotherapy have been largely unsuccessful and have therefore not been implemented in oncological practice.

Thus, there is an urgent need for development of predictors of both therapy response and toxicity. The aim of the present project is to identify and validate such markers. These will then be further studied in large prospective trials which can be initiated by members of the consortium outside the present project. If successfully validated, predictors could then be implemented in clinical practice and contribute to a new standard of care. This would benefit the individual patients by allowing individualised treatment maximising the likelihood of anti-tumour effects while minimising the risk of unnecessary toxicity.

An even more ambitious goal of the project is to identify novel modulators of drug resistance based on validated mechanisms of resistance. Initial preclinical investigations of such novel modulators are planned in the project. If successful, such novel modulators might enter clinical development outside the present project.

Summary of the CHEMORES Activity Report Period 1


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