UHN COMBIEL

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Research at Princess Margaret Hospital
University Health Network
610 University Ave
Toronto, M5A 3W7
Canada

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Project 1: REAL-PDX & NERO

REAL-PDX

Resistance modeling in EGFR and ALKLung cancer Patient-Derived Xenografts for personalized post-progression therapy 

 NERO

Non-small cell lung cancer with EGFR and Rearranged molecular alterations for Organoid models

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Main Hypothesis

The overarching hypothesis in AMP-PEL is that clinically meaningful integration of personalized cancer care is unlikely to be derived from single biomarkers, but instead will likely involve multiple biomarkers, especially those that are multi-modal, i.e., a combination of biomarkers derived from both clinico-epidemiologic and bio-molecular sources. 

Project 2: COS-ILCCO

Clinical Outcomes Studies of the International Lung Cancer Consortium Studies of Clinical Outcomes

Project 3: 2BLAST

 Biostatistical and Bioinformatic Longitudinall

Assessment of Symptoms and Toxicities

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BIOMARKER PIPELINE

The laboratory follows a rigorous biomarker development pipeline that uses the acronym, ACCE: Analytical validity, Clinical validity, Clinical Utility, and Ethics/legal/societal implications. All different modalities of biomarkers are included for analysis. 

Biomarkers studied in my laboratory have had important impact at different levels of clinical patient management: 

 

  1. Tumour Pharmacogenomics through in vivomouse modelsand organdie models (see REAL-PDX and NERO).  

The laboratory of Dr. Liu works closely with the laboratory of Dr. Ming Tsao to demonstrate proof-of-principle that primary derived xenografts and organoids of the aerodigestive tract recapitulate the primary patient’s tumour molecularly and in their therapeutic responses. The two laboratories are utilizing these models to test drugs, drug combinations, and chemoradiation, in a manner that will allow clinicians to select potentially optimal therapies for the corresponding patients who carry these tumours.

 

  1. Germline pharmacogenetic, risk, prognostic and toxicity markers.

The laboratory has identified and/or validated series of biomarkers across a dozen publications involving the platinum, EGFR, and VEGF targeting pathways, which are being validated in additional large-scale clinical trial datasets.

 

For germline markers of cancer risk and cancer prognosis, our laboratory has published over 20 manuscripts of germline prognostic markers in head and neck cancer, esophageal cancer, and lung cancer, in addition to participation or leadership in over two dozen consortia-based cancer risk and outcomes analyses publications (see COS-ILCCO). In addition to efficacy outcomes such as survival and treatment response, a new but important area of interest are symptoms and toxicities; understanding the nature of symptom and toxicity complexes are an important step forward, followed by developing predictors of symptoms and toxicities in cancer patients (see ON-PROST and 2BLAST).

 

These manuscripts are the basis of the development of multimodal biomarker prediction models that will incorporate multiple biomarkers. 

 

  1. Serologic markers

The laboratory has identified mesothelin as an excellent marker of tracking mesothelioma therapeutic responses, fibulin-3 as a high sensitivity/high specificity serologic biomarker of mesothelioma diagnostics, and plasma osteopontin as a serologic biomarker of mesothelioma prognosis. Such markers are now being studied prospectively in the clinical and clinical trial setting.

 

  1. Cell-free DNA has been evaluated for global epigenomics

This research is being conducted in collaboration with the laboratories of Rayjean Hung, Scott Bratman, Michael Hoffman and Daniel De Carvalho (see CALIBRE – liquid biopsy).

 

  1. Clinical Prognostic Markers 

The laboratory has identified and validated a number of important clinical prognostic factors, such as smoking and alcohol intake, body mass index, and comorbidity; these factors should be taken into account when specific cancer biomarker analyses are performed. Current efforts are to understand the nature prognostic factors across worldwide populations (see COS-ILCCO).