Analysis of patient mutation space and clinical outcome

Coordinator:		Prof. Dr. Jürgen Wolf
Institution:		Universitätsklinik Köln
Homepage:		www.uk-koeln.de

Lung cancer is still the most frequent cause of cancer related death worldwide.  Despite the introduction of new chemotherapeutic agents the disastrous 2 year survival rate of only about 15% has not strikingly changed during the last decades.  Recently, a new class of therapeutic agents, acting on specific targets defined on the molecular level (targeted drugs) is evaluated clinically in lung cancer; several of them have already been approved.  Although the clinical introduction of targeted drugs without doubt represents the most convincing example for translating genetic knowledge into cancer therapy, survival times so far are comparable to those under treatment with chemotherapy and thus do not represent a true breakthrough for patients.  In order to substantially improve the therapeutic success of lung cancer patients treated with defined targeted drugs pre-therapeutic identification of patient subpopulations is required.  The specific aim of this subproject is to build the groundwork for an individualized treatment of lung cancer patients by providing clinically annotated lung cancer specimens for systematic analysis of molecularly defined genetic alterations that can be therapeutically exploited.  In view of the rapidly increasing knowledge of genetically defined targets on the one hand and the continuously increasing number of targeted drugs ready for clinical evaluation on the other hand, a personalized cancer medicine, based on genetic diagnosis, is close to realization.  A precondition for the development of genetically tailored therapy of lung cancer is genetic analysis of tumor tissue performed on the highest quality level and fast enough to allow therapeutic decision based on genetic findings (real time genetic diagnosis).  Moreover, for realization of such a tailored treatment approach a close interaction between clinical oncologists, surgeons, pathologists, statistician, geneticists and basic scientists is an absolute requirement.  
To achieve these goals we will focus on the following steps:  
•    Integrated evaluation of in depth genomic analysis and phenotype of 200 NSCLC cases.
•    Prospective collection of tumor tissue, normal tissue and clinical data from patients with lung cancer and optimization of tissue preparation for genomic analyses.
•    Establishment of a re-biopsy program for lung cancer.
•    Continuous correlation of genetic and clinical information of newly acquired lung tumor samples.
•    Initiation of an exploratory clinical trial for personalized targeted therapy of relapsed NSCLC patients based on the detection of predefined genetic alterations.