PGxMTB — Implementation of Pharmacogenomics (PGx) into Molecular Tumor Boards (PGxMTB) in Europe: Improved prediction of PGx phenotypes using germline and tumor multiomics data

Personalised oncology has seen the development of drugs tailored to genetic variants associated with cancer biology. However, the full potential of targeted therapy remains untapped due to the predominant focus on acquired, tumor-specific alterations. Optimised cancer care must therefore integrate pharmacogenomic (PGx) principles, as adverse drug reactions affecting organ systems are influenced by the germline rather than the tumor genome. An essential prerequisite are computational pipelines for comprehensive pharmacogene analysis, taking into account germline data and PGx guidelines, complemented by multi-layered pharmacogene data from the tumor. The aim of PGxMTB is to implement PGx in molecular tumour boards (MTB). To achieve this goal, existing data from two nationwide precision oncology initiatives (DKFZ/NCT/DKTK MASTER, MAPPYACTS1/2) will be leveraged. A prototypic bioinformatics PGx pipeline tool will be refined by integrating 344 pharmacogenes relevant for cancer and supportive care medicines. Tumor entity-specific PGx expression patterns and multiomics profiles will be considered for all pharmacogenes to identify novel somatic PGx information, complemented by drug response data from MASTER. Tumor-related changes in individual liver PGx phenotypes will be assessed by liquid biopsy using liver-derived extracellular vesicles from cancer patients. The novel precision oncology PGx analysis pipeline will be validated in the independent MAPPYACTS1/2 cohorts. PGxMTB includes experts in basic/clinical PGx, precision oncology, bioinformatics/computational science, patient engagement and health economics. Patient representatives will be involved as research partners at all levels of PGxMTB. Health economics assessment of PGx implementation in MTB will consider different health care systems. Collectively, we expect that PGxMTB will advance PGx-driven precision cancer medicine and improve outcomes for patients.