Genomics of drug sensitivity / Precision medicine
We use omics profiling of primary cancer cells to understand the individual make-up of different diseases and individual tumors. We use this information to identify new therapeutic targets and stratification tools to develop precision medicine for patients with all types of hematologic malignancies, particularly lymphoid neoplasms (e.g. CLL, HCL). We develop clinical protocols and guidelines to position biomarkers into clinical routine. It is our vision that a detailed map of individual tumors will ultimately lead to better treatments for cancer patients – one patient at a time.
Omar-Abdel-Whahab, MSKCC, NY, USA
Wolfgang Huber, EMBL, Heidelberg, Germany
Frederic Damm, Charite, Berlin, Germany
Olivier Bernard, INSERM, Paris, France
Christopher Oakes, OSU, Columbus, USA
Next generation precision medicine for patients with Leukemia and Lymphoma/Myeloma
To develop rational and biology-based ways for patient benefit from advances in molecular understanding and targeted drug treatment, we pursue an innovative strategy based on the comprehensive mapping and understanding of individual cancers' vulnerability to compounds, pathway inhibitors and drugs as well as genome-wide silencing triggers (RNAi, CRISPR).
We systematically map pathway sensitivity (and resistance) of primary tumor cells ex vivo using diverse and relevant compound library across leukemia and lymphoma. By analyzing response patterns of sensitivity and resistance, we group tumors functionally, by response phenotype. In parallel, we directly associate and understand drug actions and their variability by investigating the underlying (causative) genetic or epigenetic changes, critical pathway activation, metabolic changes, the biology of the cell of origin and the microenvironment. Following the identification of clinically actionable vulnerabilities on primary tumors, we will mechanistically validate these with in vitro (incl. RNAi) and in vivo models and develop rational starting points for clinical development. We classify disease based on pathway sensitivity and the systematic understanding of underlying molecular networks.
Wolfgang Huber, EMBL, Heidelberg, D
Thomas Oellerich, NIH, Bethesda, USA
Jean-Pierre Bourquin, Kinderspital, Zürich, CH
Drug resistance & p53
Over the last years, we have contributed to the understanding how mutations contribute to lymphomagenesis. One particular focus of the group has been to define the role of the p53 pathway and particular mutant p53 in lymphoma. In addition to the assessment of molecular and clinical consequences of these genetic lesions, we focus on the identification of alternative drivers of disease traits such as the regulation of drug target expression (CD20), p53 degradation and gain-of-function.
Moshe Oren, Weizmann Institute, Rehovot, Israel