Ming-Sound Tsao

Dr. Tsao is a Consultant Thoracic Pathologist and Senior Scientist at the Princess Margaret Cancer Centre, University Health Network, Professor of Laboratory Medicine and Pathobiology, and the M. Qasim Choksi Chair in Lung Cancer Translational Research at the University of Toronto.

Dr. Tsao received his B.Sc. from the Simon Fraser University and M.D. from the University of British Columbia.

He trained as an Anatomic Pathologist at McGill University, and as an experimental pathologist at the University of North Carolina School of Medicine at Chapel Hill. He was a past faculty member in the Department of Pathology at McGill University and the Montreal General Hospital, Montreal, Canada.

Dr. Tsao is a member and Past Chair of the IASLC Pathology Committee, a member of the IASLC Staging and Prognostic Factor Committee, and a co-editor of the IASLC Atlas of ALK Testing in Lung Cancer. He was a past Associate Editor of the Journal of Thoracic Oncology and past Editorial Board member of the Journal of Clinical Oncology.

Dr. Tsao is the Chair of the Correlative Science and Tumor Biology Committee of the NCIC Clinical Trials Group.

He has published more than 400 peer-reviewed manuscripts.

His clinical and translational research interests include prognostic and predictive factors, including gene expression signature and genomic pathology in non-small cell lung cancer, and standardization of molecular testing in lung cancer.

Dr. Tsao was the recipient of the 2015 Mary Matthews Pathology Award from the International Association for the Study of Lung Cancer (IASLC), and the 2011 O. Harold Warwick Award from the Canadian Cancer Society and became a Fellow of the Royal Society of Canada in 2020.

Research Synopsis: the Tsao Lab

The Tsao Laboratory is focused on translational research projects in lung and pancreatic cancer at the Princess Margaret Cancer Centre (formerly known as the Ontario Cancer Institute), the largest cancer research and treatment facility in Canada and one of the top 5 cancer research centres in the World.

The lab is based in the MaRS Centre, Princess Margaret Cancer Research Tower, 14-401, 101 College Street, Toronto, Ontario, Canada M5G 1L7.

The primary goals of our lung cancer projects are to identify novel genes or proteins that are better than clinical predictors alone in predicting clinical outcome or response to therapies.

We profile the gene expression and genomic aberrations of a large number of human lung cancer samples using microarray techniques, apply computational bioinformatic algorithms to identify the predictive genes or gene signatures, and validate them by realtime quantitative PCR techniques.

The biological functions of the predictive genes are then studied using in vitro lung cancer cell line models, primary lung cancer xenograft models and orthotopic rodent models of human lung cancers.

The primary goal of our pancreatic cancer project is to dissect the molecular basis of human pancreatic cancer, which mostly arises from the duct epithelium.

Our laboratory was the first to establish primary cultures of normal human pancreatic duct cells.

Immortalized cell lines derived from these primary cultures are used to study the activities of oncogenes and tumor suppressors that are commonly aberrant in pancreatic cancer.

The approach provides insights into key molecular events that may be targeted to prevent and treat pancreatic cancer.

Special interest and emphasis involve the signaling of epidermal growth factor receptor (EGFR) and Met/hepatocyte growth factor receptor.

These two growth factor signaling loops play important roles in the growth and metastasis of lung, pancreatic and colorectal cancer.

We are also investigating the role of mutations and overexpression of these genes in the biology of these cancers.

Research overview

Lung cancer (LC) and pancreatic cancer (PC) have 5-year survival rates of 16% and 5%, respectively.

Both cancers are highly metastatic, with ~65% LC and ~80% PC patients diagnosed at advanced incurable stage. Few effective targeted therapies are available to treat LC patients, and none for PC patients.

The long term goals of my research program are to improve the diagnosis and treatment of LC and PC patients, by better understanding of their biology, molecular pathology, and heterogeneity.

The overarching hypotheses are:

1. cancer cells as defined by their aberrant genomes, interact with cancer stroma matrix/fibroblasts to contribute to heterogeneity in LC/PC growth, metastasis and drug responses;
2. genes/proteins that drive malignancy in these cancers are good targets for developing novel diagnostics and therapeutics.

Using resources/models we have developed, we will address 3 key areas of research priorities in LC and PC:

1. Tumor cell-stroma/matrix interactions driving malignancy in LC and PC

There is strong evidence that carcinoma associated fibroblasts (CAFs) and extracellular matrix (ECM) play crucial roles in cancer development, but the mechanism is still poorly understood.

The main goals of this aim is to study the complex interactions between matrix proteins and their receptors and the impact on tumor growth and metastasis.

Our studies have focused on integrin alpha 11, a receptor for fibrillar collagens, and dissecting functional or phenotypic heterogeneity among CAFs.

2. Genes and pathways driving LC and PC malignancy

Our primary goal in LC research has been to identify genes or proteins that are predictive of poor prognosis in lung cancer patients who have had their tumors resected by surgery.

We use established LC cell lines as in vitro models, large number of patient-derived xenografts (PDX) as in vivo models, snap-frozen and paraffin embedded human lung cancer tissues as primary tumor model, and orthotopic implantation of lung cancer cells in immune deficient mice as in vivo model to evaluate the biology and metastatic potential of lung cancer cells.

Patient or PDX tumor samples are used to identify tumor-associated mutations, gene expression changes and gene copy number aberrations that correlate with poor clinical outcome.

Additional functional studies are performed on cell lines with different metastatic potential.

Similar approaches are used to study the molecular basis of pancreatic duct cells carcinogenesis and metastatic progression.

These studies are conducted using a unique near normal human pancretic duct epithelial (HPDE) cells, a large number of pancreatic PDX models and their cell lines. 

3. Targetable pathways and mechanisms of resistance to targeted therapies

The diversity and complexity of genetic/phenotypic aberrations in LC and PC may underlie the challenge of target therapies.

Using the large number of PDX models and matching organoids lines derived from these genomically characterized PDX and patient tumors, we are identifying more effective biomarkers to personalized the treatment of LC/PC patients, and to mitigate/overcome the development of resistance to targeted therapies.

Selected Publications

Navab R, Strumpf D, To C, Pasko E, Kim KS, Park CJ, Hai J, Liu J, Jonkman J, Barczyk M, Bandarchi B, Wang YH, Venkat K, Ibrahimov E, Pham NA, Ng C, Radulovich N, Zhu CQ, Pintilie M, Wang D, Lu A, Jurisica I, Walker GC, Gullberg D, Tsao MS. Integrin α11β1 regulates cancer stromal stiffness and promotes tumorigenicity and metastasis in non-small cell lung cancer. Oncogene. 2016 Apr 14;35(15):1899-908. [PMID: 26148229]

Stewart EL, Mascaux C, Pham NA, Sakashita S, Sykes J, Kim L, Yanagawa N, Allo G, Ishizawa K, Wang D, Zhu CQ, Li M, Ng C, Liu N, Pintilie M, Martin P, John T, Jurisica J, Leighl N, Neel BG, Waddell TK, Shepherd FA, Liu G, Tsao MS. Clinical Utility of Patient Derived Xenografts to Determine Biomarkers of Prognosis and Map Resistance Pathways in EGFR-Mutant Lung Adenocarcinoma. J Clin Oncol. 2015 Aug 1;33(22):2472-80.[PMID: 26124487]

Tsao MS, Travis WD, Brambilla E, Nicholson A, Noguchi M, Hirsch FR, on behalf of the IASLC Pathology Committee. Forty years of the International Association for Study of Lung Cancer Pathology Committee. J Thorac Oncol 2014 Dec;9(12):1740-9. [PMID:25393791]

Radulovich N, Leung L, Ibrahimov E, Navab R, Sakashita S, Zhu C-Q, Kaufman E, Lockwood WW, Thu KL, Fedyshyn Y, Moffat J, Lam WL, Tsao MS. Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma. Oncogene. 2014 Aug 6;34(32):4238-47. [Epub ahead of print] [PMID:25381825]

Cancer Genome Atlas Research Network. (One of 383 collaborators). Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014 Jul 31;511(7511):543-50. [PMID: 25079552]

Cescon DW, She D, Sakashita S, Zhu CQ, Pintilie M, Shepherd FA, Tsao MS.  NRF2 pathway activation and adjuvant chemotherapy benefit in lung squamous cell carcinoma. Clin Cancer Res. 2015 Jun 1;21(11):2499-505. PMID: 25739673

Golaraei A, Cisek R, Krouglov S, Navab, R, Sakashita S, Yasufuku K, Tsao MS, Niu C, Wilson BC, Barzda V. Characterization of collagen in non-small cell lung carcinoma with second harmonic polarization microscopy. Biomedical Optics Express 2014 Sep 11;5(10): 3562-3567.  PMID: 25360372

Cancer Genome Atlas Research Network. (One of 383 collaborators). Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014 Jul 31;511(7511):543-50. [PMID: 25079552]

Der SD, Sykes J, Pintilie M, Zhu CQ, Strumpf D, Liu N, Jurisica I, Shepherd FA, Tsao MS. Validation of a Histology-Independent Prognostic Gene Signature for Early-Stage, Non-Small-Cell Lung Cancer Including Stage IA Patients. J Thorac Oncol. 2014 Jan;9(1):59-64. PMID:24305008

Sakashita S, Sakashita M, Tsao MS. Genes and pathology of non-small cell lung carcinoma. Semin Oncol. 2014 Feb;41(1):28-39. PMID: 24565579

IASLC ATLAS of ALK Testing in Lung Cancer, M.S. Tsao, F.R. Hirsch, Y. Yatabe (Editors), International Association for the Study of Lung Cancer (IASLC) Dec 16, 2013.

Goss GD, O'Callaghan C, Lorimer I, Tsao MS, Masters GA, Jett J, Edelman MJ, Lilenbaum R, Choy H, Khuri F, Pisters K, Gandara D, Kernstine K, Butts C, Noble J, Hensing TA, Rowland K, Schiller J, Ding K, Shepherd FA. Gefitinib versus Placebo in Completely Resected Non-Small-Cell Lung Cancer: Results of the NCIC CTG BR19 Study. J Clin Oncol. 2013 Sep 20;31(27):3320-6. PMID: 23980091

Yanagawa N, Leduc C, Kohler D, Saieg MA, John T, Sykes J, Yoshimoto M, Pintilie M, Squire J, Shepherd FA, Tsao MS. Loss of phosphatase and tensin homolog (PTEN) protein expression is an independent prognostic marker in lung adenocarcinoma. J Thorac Oncol 2012 Oct;7(10):1513-1521. PMID: 22982652

Saieg MA, Geddie WR, Boerner SL, Liu N, Tsao M, Zhang T, Kamel-Reid S, da Cunha Santos G. The use of FTA cards for preserving unfixed cytological material for high-throughput molecular analysis. Cancer Cancer Cytopathol. 2012 Jun 25;120(3):206-14. PMID: 22275131

Navab R, Strumpf D, Bandarchi B, Zhu CQ, Pintilie M, Ramnarine VR, Ibrahimov E, Radulovich N, Leung L, Barczyk M, Panchal D, To C, Yun JJ, Der S, Shepherd FA, Jurisica I, Tsao MS. Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7160-5.  PMID: 21474781   

Appointments

Consultant Thoracic Pathologist, Princess Margaret Cancer Centre, University Health Network
Senior Scientist, Princess Margaret Cancer Centre, University Health Network
Chair, Correlative Science and Tumor Biology Committee, NCIC Clinical Trials Group

Honours and Awards

LMP Outstanding Mentor Award, University of Toronto (2022)

LMP Richard G. Hegele Award for Excellence in Research and Innovation, University of Toronto (2022)

Fellow of the Canadian Academy of Health Sciences (CAHS) 2021

Fellow of the Royal Society of Canada (2020)

M. Qasim Choksi Chair in Lung Cancer Translational Research

Mary Matthews Pathology Award, International Association for the Study of Lung Cancer (IASLC) (2015)

O. Harold Warwick Award from the Canadian Cancer Society (2011)