Geoffrey Liu

Research Synopsis

Pharmacogenomic epidemiology is a research area that utilizes epidemiologic methodologies to interrogate pharmacogenomic questions. This research focuses on the use of observational datasets or secondary analyses of clinical trials to evaluate the impact of genetic variation and tumour genomics within pharmacodynamic and pharmacokinetic pathways of therapies on important patient outcomes, such as treatment response, survival or toxicity.

The Liu laboratory, known as AMPPEL (Applied Molecular Profiling Pharmacogenomic Epidemiologic Laboratory) involves a wet component (cell line, primary human xenografts, and primary human tissues, functional assays) and a dry laboratory (clinic-epidemiologic recruitment, data collection, sample acquisition, statistical analysis, epidemiologic and health services outcomes research analyses). The application of molecular epidemiologic methods to pharmacogenetics has provided new opportunities to evaluate rigorously the role of genomic factors in cancer treatment outcomes and toxicity. When large clinical trials involving the drugs of interest are available, secondary analysis of such trials is the preferred method of studying pharmacogenetics. However, there are many instances, such as in rare tumours or when trying to evaluate pharmacogenomics of standard chemotherapy or radiotherapy treatments, where clinical trials are not available to answer important pharmacogenetic questions. Under these circumstances, the role of carefully planned prospective observational studies becomes instrumental to answer both pharmacogenomic and cancer prognosis questions. The quality of results obtainable from these studies is highly dependent on the methods used to recruit patients, to obtain and process samples, to accurately measure genetic markers, to determine accurate phenotypes and outcomes, and to perform appropriate statistical analysis. In addition, pharmacogenomic functional assays and testing are an important component. Therefore, PGE results from these high quality observational studies and clinical trials, the goal of much of AMPPEL's efforts, have strong potential to impact on patient risk stratification and in the choice of appropriate therapies. Dr. Liu is the overall lead PI of the CARMA BROS study (Canadian Rare Molecular Alteration Basket-umbrella Real-world Observational Study; NCT04151342), and site PI of PALEOS (Pan-Canadian Lung cancEr Observational Study; NCT04706754).