Dr. Liu graduated sum laude from the University of Toronto medicine program, followed by residencies at the University of Toronto and a fellowship at the Dana Farber Harvard Cancer Center in Boston. He was Assistant Professor of Medicine at Harvard Medical School before returning in 2006 to the Ontario Cancer Institute–Princess Margaret Hospital. Dr. Liu’s major research focus is in molecular prognostic factors and pharmacogenomics of lung and esophageal cancer, with additional interest in head and neck, pancreatic, ovarian and testicular cancers, mesothelioma and thymoma. Trained in clinical and molecular epidemiology, he is the principal investigator of over two dozen completed, ongoing and upcoming cancer pharmacogenomic and molecular epidemiologic analyses of cancer observational studies and clinical trials funded by the National Cancer Institute (US), National Cancer Institute of Canada Clinical Trials Group, Canadian Cancer Society Research Institute, the Canadian Institute of Health Research, the Ontario Institute of Cancer Research, Cancer Care Ontario, Doris Duke Foundation and the Lung Cancer Foundation of America. He has research interests in epidemiological outcomes database methods, novel analyses of high dimensionality biologically rich data, pharmacogenomic analyses of conventional and molecularly targeted agents using primary human xenograft models, patient-reported outcomes in pharmacogenomics, and knowledge translation of personalized medicine and pharmacogenomic algorithms into clinical practice.
- Pharmacogenomic epidemiology (PGE)Pharmacogenomic epidemiology is a relatively new 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.
- AMPPEL dry laboratoryA major impediment to performing PGE research has been the lack of systematic collection of toxicity outcomes outside of the clinical trial setting. Dr. Liu is co-director of the ON-PROST ACRU (Ontario Patient Reported Outcomes of Symptoms and Toxicity Applied Clinical Research Unit) funded by Cancer Care Ontario (CCO). This clinical research unit is envisioned as a virtual laboratory for piloting different methods for systematically collecting patient symptoms and toxicity as part of routine care and for research purposes, developing province-wide consensus on what toxicities and symptoms to collect, to support the computer adaptive technology required for province-wide implementation. The majority of pilots are beginning at PMH (lung, head and neck, gastro-esophageal, testicular cancers), in areas that correspond to ongoing molecular epidemiological studies. Dr. Liu also holds a CCO Chair which supports research into exploring the feasibility, assessing the accuracy and developing a proper pipeline to obtain and link CCO and ICES (Institute of Clinical Evaluative Sciences) database information on systemic/radiation therapy with our PMH study specific databases in lung, gastroesophageal and pancreatic cancers.
Evaluations of Clinical Utility and Clinical Uptake of pharmacogenomic testing are critical to translation from bench to bedside. In the era of personalized medicine, evaluating whether patients understand what pharmacogenomic testing means and involves, their attitude and preferences is important. Through interview-based research utilizing theoretical scenarios and either trade-off testing or conjoint testing, AMPPEL has been ascertaining PMH patient and physician attitudes, understanding and preferences for pharmacogenetic testing.
- AMPPEL wet laboratoryAMPPEL is performing PGE evaluations in clinical trials and observational studies, using archival tissue, fresh tissue, blood and other surrogate tissues. The methodologic approaches used include: candidate-based analyses, pharmacokinetic (PK) and pharmacodynamic (PD) pathway analyses, genome-wide association studies (GWAS) and post-GWAS analyses (includes methods development), and in the next few years, Next Generation Sequencing (Whole Exome, Whole Genome Sequencing). In addition, AMPPEL recruits hundreds of patients into molecular epidemiologic studies, including patients with Lung, Head and Neck, Gastro-esophageal, hepatobiliary, pancreatic, and testicular cancer patients, thymomas and mesotheliomas. The laboratory has helped to integrate and coordinate consenting, recruitment, data collection, data management, quality control and clinico-epidemiologic analyses for multiple cancer site
The Gastro-esophageal Cancer Primary Xenograft Program: AMPPELs pharmacogenomic research also developed and utilizes mouse xenografts carrying primary human gastro-esophageal tumours (obtained during biopsy and resection). These xenografts have been treated with conventional chemotherapy, radiation, and chemoradiation, expanding to the use of novel targeted agents (with or without radiation). Thus, this research involves the evaluation of pharmacogenomic and radiogenomic changes during treatment of these xenografts, characterization of these xenografts for various oncogenic and tumour suppressor gene pathways and evaluation of molecular targeted agents in these xenografts. This set of primary human cancer derived xenografts is a unique resource, given the paucity of esophageal adenocarcinoma cell lines.
Radiogenomics: Given the importance of radiation and chemoradiation in many of AMPPELs primary disease sites (head and neck cancer, gastroesophageal cancer, lung cancer, pancreatic cancer), research in AMPPEL evaluates the role of genomics and genetics of normal tissue toxicity after radiation. Along with colleagues in Quebec, AMPPEL has completed the first ever genome-wide association study (GWAS) of radiogenetics in head and neck cancer patients treated solely with radiation, a secondary analysis (CCSRI funded, co-PI Liu) of a secondary prevention trial.
Lung Cancer Early Detection and Prevention Biomarker Program: The specific focus of this research is to identify biomarkers that can refine the selection for CT screening, identify biomarkers that identify patients for specific interventions and develop risk stratification that incorporates biomarkers. Since 2009, Dr. Liu has collaborated with Dr. Reisman of the University of Florida on the Brahma-HDAC pathway polymorphisms as potential biomarkers of risk and primary prevention intervention.
Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.
Clin Gastroenterol Hepatol. 2018 Mar 15;:
Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants.
Gastroenterology. 2017 Dec 13;:
Further investigation of the role of ACYP2 and WFS1 pharmacogenomic variants in the development of cisplatin-induced ototoxicity in testicular cancer patients.
Clin Cancer Res. 2018 Jan 22;:
Mol Carcinog. 2018 Jan;57(1):106-113
Molecular Profiling of Patients With Advanced Colorectal Cancer: Princess Margaret Cancer Centre Experience.
Clin Colorectal Cancer. 2017 Oct 23;:
J Minim Invasive Gynecol. 2017 Oct 24;:
Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.
Carcinogenesis. 2017 Oct 20;:
Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.
Lancet Oncol. 2017 Oct 16;:
A phase I study of foretinib plus erlotinib in patients with previously treated advanced non-small cell lung cancer: Canadian cancer trials group IND.196.
Oncotarget. 2017 Sep 19;8(41):69651-69662
Senior Scientist, Princess Margaret Cancer Centre
Alan B. Brown Chair in Molecular Genomics
CCO Chair in Experimental Therapeutics and Population Studies
Director, Applied Molecular Profiling Pharmacogenomic Epidemiologic Laboratory, PMH
Co-Director, Ontario Patient Reported Outcomes of Symptoms and Toxicity
Co-Director, COMBIEL Training Initiative
Associate Professor, Epidemiology, Dalla Lana School of Public Health