Molecular Stratification of Somatic and Hereditary Cancers
A central goal of NCT is molecularly guided patient stratification as the basis for individualized treatment decisions in somatic and hereditary cancers. By leveraging the expertise of NCT, DKFZ and DKTK in multidimensional tumor characterization and molecular mechanism-based therapy, NCT has developed a standard for (1) comprehensive molecular profiling, (2) clinical interpretation of molecular data, (3) functional analysis of primary patient samples, (4) treatment decision making in molecular tumor boards, (5) longitudinal clinical data collection and (6) clinical trial design and conduct. This pipeline provides a framework for multiple clinical programs and is intertwined with translational research projects centered on understanding the functional consequences of molecular alterations, with the ultimate goal to incorporate functional genomic profiling and ex vivo treatment testing in the precision oncology workflow.
Research Profile Dresden
Personalized oncology through molecular stratification at NCT/UCC Dresden combines in-depth genomic characterization of tumor and germline with additional layers of clinical specimen characterization. Broad subgenomic sequencing at the Core Unit for Molecular Tumor Diagnostics (CMTD) and comprehensive profiling within the MASTER program, the “Modellvorhaben Genomsequenzierung” and the RATIONAL trial are provided. The newly established Preclinical Model Unit systematically develops and generates organoid and spheroid models for the functionalization of genomic alterations, drug testing, and functional screening supported by extensive expertise in Dresden. Exosomes and circulating tumor cells are explored as biomarkers for drug response and resistance in glioblastoma, gastrointestinal, and gynecological cancers
Comprehensive genomic sequencing for molecularly-guided treatment
Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancersJahn et al. explored the therapeutic relevance of germline variant evaluation in precision oncology of rare cancers and how it opens new paths toward the identification of patients with genetic tumor risk syndromes. They identified a relevant percentage of patients that harbored previously unknown germline variants in relevant cancer predisposition genes, some of which additionally supported treatment recommendations, whose implementation led to a clinical benefit in 40% of treated patients.
Jahn et al. Ann Oncol 2022
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Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularlyinformed therapies despite heterogeneity
Möhrmann et al used comprehensive molecular characterization by whole genome/exome, transcriptome and methylome analysis in 70 CUP patients to descibe a heterogeneous molecular landscape revealing molecular targets relevant for treatment. Recommended off-label therapies translate into a mean PFS ratio of 3.6 with a median PFS1 of 2.9 months and a median PFS2 of 7.8 months. The data emphasizes the clinical value of molecular analysis and underline the need for innovative, mechanism-based clinical trials.
Möhrmann et al. Nat Commun 2022
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Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
Horak et al analyzed whole-genome/exome and RNA sequencing-based molecular profiles and clinical outcomes of 1,310 patients. Based on 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment. Recommended therapies resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared to previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients.
Horak et al Cancer Discov 2021
>>> OCT2 Trial: Randomized Comparison of Treatment Guided by Comprehensive Genome and Transcriptome Analysis versus Standard of Care in Patients with Advanced Rare Cancers (RATIONALE)
>>> Proof of Concept Trial: DEcision support by ClusterIng based on SImilarity measures in precision Oncology of Neuroendocrine neoplasia and Sarcoma (DECISIONS)