CURELUNG · Determining (epi)genetic therapeutic signatures for improving lung cancer prognosis

Lung cancer (LC) is still the most lethal type of cancer worldwide. The extremely poor prognosis for LC patients is partly due to the lack of effective therapies. At present, most patients with pulmonary carcinomas are treated with chemotherapy. This essentially consists of classic cytotoxic drugs which only improve survival in small cohorts in few cases. In spite of the rapidly growing understanding of the epigenetic and genetic profile of LC, such knowledge has contributed little to improving therapeutics. This scenario, however, is likely to change soon because several specific cancer therapies, targeting molecules that are altered in cancer, are being developed or are already undergoing clinical trials. Thinking ahead, our proposal focuses, on the one hand, on validating novel and specific therapeutic strategies, with particular emphasis on discovering (epi)genetic alterations that could act as novel targets for therapies, and, on the other, on defining the (epi)genetic markers that could determine the efficacy response or resistance to targeted therapies as well as the acquired resistance of the tumours to therapy. To reach our goals, we have designed an integrative and interdisciplinary approach involving leading European clinical scientists of international renown with prominent preclinical and basic research groups using high throughput and state-of-the art platforms for genomics and gene expression analysis. To date, no such comprehensive information exists. The results will be of great value for the stratification of lung tumours according to their genetic background for tailored treatments. The development of an (epi)genetic-based therapeutic prediction model will hopefully set the basis for future tailored treatment of LC as well as of other epithelial cancers.