The mission of this Cancer Network is to reduce the burden of cancer through exploration, discovery and the exploitation of the most modern tools of research furnished by genomic insights. These aims are being achieved through interdisciplinary basic and clinical research, translational research, technology development and the creation of partnerships between clinics and academia.
The Cancer Network is composed of over 40 principal investigators and takes advantage of the exceptional possibilities offered by the wide range of tools and expertise within the NGFN to foster interdisciplinary collaborations and progress within cancer research. Basic researchers interact closely with clinicians involved in the design and conductance of clinical trials. Areas of excellence include expression profiling, molecular targets of cancer, molecular imaging, biological mediators, cancer prevention, angiogenesis and molecular pathology of breast and colon cancer and leukemias.
The Cancer Network seeks to translate scientific knowledge towards achieving more effective cancer prevention, intervention and treatment. The Cancer Network is committed to forming partnerships that encourage joint research efforts with industry and academic institutions to accelerate the pace of medical research.
The major impact of many genes on cancer development and progression was initially identified in pediatric cancers. The early cancer manifestation suggests that only a limited number of genetic changes lead to the transformed phenotype, making embryonal tumors an ideal model for the investigation of cancer-related molecular pathways.
The embryonal tumor neuroblastoma (NB) is derived from the sympathetic nervous system and represents the most common extracranial solid tumor in young children. Treatment with polychemotherapy provokes a good initial response. However, on the one hand disseminated stage 4 tumors frequently relapse due to minimal residual disease with a few resistant tumor cells, resulting in poor overall survival rates (<35%). On the other hand, overtreatment of MYCN-negative stage 2 or 3 tumors is a major problem. Most surviving patients will have suffered from significant organ toxicity or development of secondary malignancies. Thus, novel treatment approaches are urgently needed. To this end, we conduct a comprehensive program to explore the systems biology of neuroblastoma, unravelling its malignant features by high-throughput genomic and proteomic technologies as well as functional analysis of previously identified target genes in the major fields of interest. The network can rely on the established nationwide clinical neuroblastoma database and central tumor bank for embryonal tumors, using well-defined SOPs and covering >90% of all German neuroblastoma patients.
A tremendous amount of genomic data regarding the systems biology of NB has already been obtained within the first funding period of the National Genome Research Network (NGFN-1) and the Human Genome Project. These data will now be validated and utilized for the improvement of neuroblastoma treatment using two different strategies:
(1) Precise definition of the individual risk of relapse for each patient to individually adjust treatment intensity
(2) Identification of new drug targets to develop well-tolerated, disease- and patient-adapted antitumor strategies based on molecular information. The resulting biological insights should serve as a model for other malignant diseases.
Due to their localization and limited accessibility, treatment of cranial tumors is often very difficult and requires cooperation of multiple medical disciplines. Biologically, this heterogeneous group of cancers is characterized by high relapse rates. The identification of prognostic markers, that allow prediction of tumor recurrence, would serve a pressing clinical demand.
Comprehensive molecular profiling will yield in
i) new prognostic markers
ii) support refinement of tumor classification schemes
iii) elucidate tumor pathomechanisms, which will be the basis for the definition of novel therapeutic interference points.
A long-term interdisciplinary approach is required to develop novel diagnostic and treatment tools for these grave malignancies.
Our Cranial Cancer Network will combine functional genomic profiling approaches and two established consortia of clinical researchers investigating head and neck squamous cell carcinoma, malignant glioma and retinoblastoma. Profiling will include DNA methylation, DNA copy number changes, as well as RNA and protein expression. Combination of these data sets from the same series of tumors will create strong synergistic effects. Bioinformatic analysis, utilizing a novel dedicated data base, allows integration of molecular and clinical data.
Each of the disease oriented consortia investigates well-defined series of existing core tumor collections. Interactions between these are fostered by the related scientific questions addressed in each package. These include
(i) DNA methylation status
(ii) the identification of activated oncogenes and inactivated tumor suppressorgenes and respective gene products