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Princess Margaret Living Biobank

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Welcome to UHN Princess Margaret Living Biobank

The PM Living Biobank at the Princess Margaret Cancer Centre is a collaboration between PM researchers and UHN Biospecimen Core to establish a central repository and provide services for the use of patient-Derived tumor Organoid (PDO) and Xenograft (PDX) models.

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Our Services

  • checkmarkPDO/PDX model establishment
  • checkmarkPDO/PDX model annotation with essential clinical information and molecular profiling
  • checkmarkBiomarker-directed studies and drug testing on PMLB PDO/PDX models
  • checkmarkCustom contracted projects
  • checkmarkGrant support
  • checkmarkModel distributions (UHN and external UHN)
  • checkmarkProvide SOPs; organoid/xenograft training

Organoid Services

  • checkmarkOrganoid consumables (e.g. organoid and conditioned media)
  • checkmarkGenome editing of organoid models

Core

Icon image of dna

PMLB PDX Core

What is PDX?

PDX models are increasingly being recognized as clinically more relevant models to identify the phenotype-genotype association in patient tumors and to discover drug response and resistance biomarkers. PDXs mirror the histopathological features and genetic profiles of the original patient tumors during early passages in immune-deficient mouse hosts.

While cancer was once thought of as a single disease that affected many different parts of the body, researchers now know that there are differences in the DNA makeup of each patient's cancer cells. These changes in cancers' DNA can cause each cancer to have unique behaviors. That's why two patients who have cancer in the same part of the body may respond differently to the same treatment. Testing for mutations and other genetic abnormalities in cancer cells is known as molecular profiling.

Why is a PDX Core Important?

Due to the high cost of model establishment, experimentation, and quality control protocols, there are ongoing efforts to unify PDX resources and processes by forming consortiums. Examples include EurOPDX, NCI Patient-Derived Models of Cancer Program, and other labs have partnered with industry.

Objectives

  • checkmarkCreate a UHN repository for existing and new tumor PDO/PDX models for researchers or public-private partnerships.
  • checkmarkEstablish standard operating protocols and use comprehensive quality control tests to implement best practices for establishing and using PDO/PDX models.
  • checkmarkProvide an integrated data search portal linking tumor models with corresponding patients, including clinical annotation, genomics, and experimental data.
  • checkmarkOffer core services, including training and turnkey studies.
Tumour Type PDX Models (count)
Lung >145
Pancreas >213
Ovarian >85
Colon >300
Head & Neck 104
Mesothelium 14
Metastases (pan-tumor) 14
Total >862

Our resource is listed in an open global catalogue of PDX models for comprehensive search and attribute filtering support for clinico-pathological and molecular data (https://www.pdxfinder.org/source/pmlb/). Molecular data and visualization of our profiled models could be accessed through our institute's portal.

Icon image of cell

PMLB Organoids

What is an Organoid?

A PDO is a three-dimensional structure grown from cancer cells in a gel-like compound using media-containing components which support renewal. PDOs are amenable to faster expansion times in culture under the appropriate conditions and result in higher throughput than PDX models. PDO models are currently available for cancer types, including colon, pancreas, and lung, and protocols for more tumor types are being developed.

Organoid models are derived from patient-derived xenograft tissues, primary tumors, and metastatic patient tissues. PMLB organoid repository includes models generated from colorectal, pancreatic, and lung cancer tissues.

  • checkmarkEach organoid model has been extensively characterized:
  • checkmarkSTR matched to patient tissue
  • checkmarkHistopathology
  • checkmarkMycoplasma testing
  • checkmarkDoubling rate
  • checkmarkOrganoid models are accessible to internal/external researchers (view available models)
  • checkmarkOMICS profiling

Example of Organoid Model Datasheet

PMLB References

Click below to view all references.

  1. Brana, I., Pham, N. A., Kim, L. et al. Novel combinations of PI3K-mTOR inhibitors with dacomitinib or chemotherapy in PTEN-deficient patient-derived tumor xenografts. Oncotarget 8, 84659, doi:10.18632/oncotarget.19109 (2017).
  2. Chang, Q., Jurisica, I., Do, T. et al. Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res 71, 3110, doi:10.1158/0008-5472.CAN-10-4049 (2011).
  3. Chia, P. L., Parakh, S., Tsao, M. S. et al. Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel) 13, doi:10.3390/ph13100289 (2020).
  4. Cybulska, P., Stewart, J. M., Sayad, A. et al. A Genomically Characterized Collection of High-Grade Serous Ovarian Cancer Xenografts for Preclinical Testing. Am J Pathol 188, 1120, doi:10.1016/j.ajpath.2018.01.019 (2018).
  5. Derouet, M. F., Allen, J., Wilson, G. W. et al. Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor. Sci Rep 10, 14514, doi:10.1038/s41598-020-71589-4 (2020).
  6. Dodbiba, L., Teichman, J., Fleet, A. et al. Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment. Lab Invest 93, 397, doi:10.1038/labinvest.2013.8 (2013).
  7. Gao, S., Soares, F., Wang, S. et al. CRISPR screens identify cholesterol biosynthesis as a therapeutic target on stemness and drug resistance of colon cancer. Oncogene 40, 6601, doi:10.1038/s41388-021-01882-7 (2021).
  8. Gebregiworgis, T., Marshall, C. B., Nishikawa, T. et al. Multiplexed Real-Time NMR GTPase Assay for Simultaneous Monitoring of Multiple Guanine Nucleotide Exchange Factor Activities from Human Cancer Cells and Organoids. Journal of the American Chemical Society 140, 4473, doi:10.1021/jacs.7b13703 (2018).
  9. Gebregiworgis, T., Kano, Y., St-Germain, J. et al. The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors. Nat Commun 12, 6274, doi:10.1038/s41467-021-26526-y (2021).
  10. Gendoo, D. M. A., Denroche, R. E., Zhang, A. et al. Whole genomes define concordance of matched primary, xenograft, and organoid models of pancreas cancer. PLoS Comput Biol 15, e1006596, doi:10.1371/journal.pcbi.1006596 (2019).
  11. Grunwald, B. T., Devisme, A., Andrieux, G. et al. Spatially confined sub-tumor microenvironments in pancreatic cancer. Cell 184, 5577, doi:10.1016/j.cell.2021.09.022 (2021).
  12. Hai, J., Sakashita, S., Allo, G. et al. Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non-Small Cell Lung Cancer Xenograft Models. J Thorac Oncol 10, 1172, doi:10.1097/JTO.0000000000000584 (2015).
  13. Hai, J., Liu, S., Bufe, L. et al. Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers. Clin Cancer Res 23, 6993, doi:10.1158/1078-0432.CCR-17-1098 (2017).
  14. Haynes, J., McKee, T. D., Haller, A. et al. Administration of Hypoxia-Activated Prodrug Evofosfamide after Conventional Adjuvant Therapy Enhances Therapeutic Outcome and Targets Cancer-Initiating Cells in Preclinical Models of Colorectal Cancer. Clin Cancer Res 24, 2116, doi:10.1158/1078-0432.CCR-17-1715 (2018).
  15. Huo, K. G., D'Arcangelo, E. & Tsao, M. S. Patient-derived cell line, xenograft and organoid models in lung cancer therapy. Transl Lung Cancer Res 9, 2214, doi:10.21037/tlcr-20-154 (2020).
  16. Huo, K. G., Notsuda, H., Fang, Z. et al. Lung Cancer Driven by BRAF(G469V) Mutation Is Targetable by EGFR Kinase Inhibitors. J Thorac Oncol 17, 277, doi:10.1016/j.jtho.2021.09.008 (2022).
  17. Hussain, A., Voisin, V., Poon, S. et al. Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21. J Exp Med 217, doi:10.1084/jem.20191094 (2020).
  18. John, T., Kohler, D., Pintilie, M. et al. The ability to form primary tumor xenografts is predictive of increased risk of disease recurrence in early-stage non-small cell lung cancer. Clin Cancer Res 17, 134, doi:10.1158/1078-0432.CCR-10-2224 (2011).
  19. John, T., Yanagawa, N., Kohler, D. et al. Characterization of lymphomas developing in immunodeficient mice implanted with primary human non-small cell lung cancer. J Thorac Oncol 7, 1101, doi:10.1097/JTO.0b013e3182519d4d (2012).
  20. Kano, Y., Gebregiworgis, T., Marshall, C. B. et al. Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation. Nat Commun 10, 224, doi:10.1038/s41467-018-08115-8 (2019).
  21. Karamboulas, C., Bruce, J. P., Hope, A. J. et al. Patient-Derived Xenografts for Prognostication and Personalized Treatment for Head and Neck Squamous Cell Carcinoma. Cell Rep 25, 1318, doi:10.1016/j.celrep.2018.10.004 (2018).
  22. Karamboulas, C. & Ailles, L. Patient-derived xenografts: a promising resource for preclinical cancer research. Mol Cell Oncol 6, 1558684, doi:10.1080/23723556.2018.1558684 (2019).
  23. Koshkin, V., De Oliveira, M. B., Peng, C. et al. Multi-drug-resistance efflux in cisplatin-naive and cisplatin-exposed A2780 ovarian cancer cells responds differently to cell culture dimensionality. Mol Clin Oncol 15, 161, doi:10.3892/mco.2021.2323 (2021).
  24. Ku, A., Chan, C., Aghevlian, S. et al. MicroSPECT/CT Imaging of Cell-Line and Patient-Derived EGFR-Positive Tumor Xenografts in Mice with Panitumumab Fab Modified with Hexahistidine Peptides To Enable Labeling with (99m)Tc(I) Tricarbonyl Complex. Mol Pharm 16, 3559, doi:10.1021/acs.molpharmaceut.9b00422 (2019).
  25. Lai Benjamin, F. L., Lu Rick, X., Hu, Y. et al. Recapitulating pancreatic tumor microenvironment through synergistic use of patient organoids and organ-on-a-chip vasculature. Adv Funct Mater 30, doi:10.1002/adfm.202000545 (2020).
  26. Li, L., Wei, Y., To, C. et al. Integrated omic analysis of lung cancer reveals metabolism proteome signatures with prognostic impact. Nat Commun 5, 5469, doi:10.1038/ncomms6469 (2014).
  27. Lima-Fernandes, E., Murison, A., da Silva Medina, T. et al. Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells. Nat Commun 10, 1436, doi:10.1038/s41467-019-09309-4 (2019).
  28. Lohse, I., Lourenco, C., Ibrahimov, E. et al. Assessment of hypoxia in the stroma of patient-derived pancreatic tumor xenografts. Cancers (Basel) 6, 459, doi:10.3390/cancers6010459 (2014).
  29. Lohse, I., Kumareswaran, R., Cao, P. et al. Effects of Combined Treatment with Ionizing Radiation and the PARP Inhibitor Olaparib in BRCA Mutant and Wild Type Patient-Derived Pancreatic Cancer Xenografts. PLoS One 11, e0167272, doi:10.1371/journal.pone.0167272 (2016).
  30. Lohse, I., Rasowski, J., Cao, P. et al. Targeting hypoxic microenvironment of pancreatic xenografts with the hypoxia-activated prodrug TH-302. Oncotarget 7, 33571, doi:10.18632/oncotarget.9654 (2016).
  31. Martin, P., Stewart, E., Pham, N. A. et al. Cetuximab Inhibits T790M-Mediated Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in a Lung Adenocarcinoma Patient-Derived Xenograft Mouse Model. Clin Lung Cancer 17, 375, doi:10.1016/j.cllc.2016.01.002 (2016).
  32. Martins-Filho, S. N., Weiss, J., Pham, N. A. et al. EGFR-mutated lung adenocarcinomas from patients who progressed on EGFR-inhibitors show high engraftment rates in xenograft models. Lung Cancer 145, 144, doi:10.1016/j.lungcan.2020.03.022 (2020).
  33. Mason, J. M., Lin, D. C., Wei, X. et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell 26, 163, doi:10.1016/j.ccr.2014.05.006 (2014).
  34. Mer, A. S., Ba-Alawi, W., Smirnov, P. et al. Integrative Pharmacogenomics Analysis of Patient-Derived Xenografts. Cancer Res 79, 4539, doi:10.1158/0008-5472.CAN-19-0349 (2019).
  35. Mirhadi, S., Tam, S., Li, Q. et al. Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes. Nat Commun 13, 1811, doi:10.1038/s41467-022-29444-9 (2022).
  36. Murillo-Sauca, O., Chung, M. K., Shin, J. H. et al. CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma. Oncotarget 5, 6854, doi:10.18632/oncotarget.2269 (2014).
  37. Nakajima, T., Geddie, W., Anayama, T. et al. Patient-derived tumor xenograft models established from samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration. Lung Cancer 89, 110, doi:10.1016/j.lungcan.2015.05.018 (2015).
  38. Notta, F., Chan-Seng-Yue, M., Lemire, M. et al. A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 538, 378, doi:10.1038/nature19823 (2016).
  39. O'Brien, C. A., Pollett, A., Gallinger, S. et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106, doi:10.1038/nature05372 (2007).
  40. O'Brien, C. A., Kreso, A., Ryan, P. et al. ID1 and ID3 regulate the self-renewal capacity of human colon cancer-initiating cells through p21. Cancer Cell 21, 777, doi:10.1016/j.ccr.2012.04.036 (2012).
  41. Ortmann, J., Rampasek, L., Tai, E. et al. Assessing therapy response in patient-derived xenografts. Sci Transl Med 13, eabf4969, doi:10.1126/scitranslmed.abf4969 (2021).
  42. Pham, N. A., Radulovich, N., Ibrahimov, E. et al. Patient-derived tumor xenograft and organoid models established from resected pancreatic, duodenal and biliary cancers. Sci Rep 11, 10619, doi:10.1038/s41598-021-90049-1 (2021).
  43. Prince, E., Cruickshank, J., Ba-Alawi, W. et al. Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids. Nat Commun 13, 1466, doi:10.1038/s41467-022-28788-6 (2022).
  44. Rehman, S. K., Haynes, J., Collignon, E. et al. Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy. Cell 184, 226, doi:10.1016/j.cell.2020.11.018 (2021).
  45. Ruicci, K. M., Meens, J., Sun, R. X. et al. A controlled trial of HNSCC patient-derived xenografts reveals broad efficacy of PI3Kalpha inhibition in controlling tumor growth. Int J Cancer 145, 2100, doi:10.1002/ijc.32009 (2019).
  46. Saraon, P., Snider, J., Kalaidzidis, Y. et al. A drug discovery platform to identify compounds that inhibit EGFR triple mutants. Nat Chem Biol 16, 577, doi:10.1038/s41589-020-0484-2 (2020).
  47. Saraon, P., Snider, J., Schormann, W. et al. Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells. J Mol Biol 433, 167294, doi:10.1016/j.jmb.2021.167294 (2021).
  48. Shi, R., Varella-Garcia, M., Li, M. et al. An Anaplastic Lymphoma Kinase Immunohistochemistry-Negative but Fluorescence In Situ Hybridization-Positive Lung Adenocarcinoma Is Resistant to Crizotinib. J Thorac Oncol 11, 2248, doi:10.1016/j.jtho.2016.08.139 (2016).
  49. Shi, R., Li, M., Raghavan, V. et al. Targeting the CDK4/6-Rb Pathway Enhances Response to PI3K Inhibition in PIK3CA-Mutant Lung Squamous Cell Carcinoma. Clin Cancer Res 24, 5990, doi:10.1158/1078-0432.CCR-18-0717 (2018).
  50. Shi, R., Filho, S. N. M., Li, M. et al. BRAF V600E mutation and MET amplification as resistance pathways of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in lung cancer. Lung Cancer 146, 78, doi:10.1016/j.lungcan.2020.05.018 (2020).
  51. Shi, R., Radulovich, N., Ng, C. et al. Organoid Cultures as Preclinical Models of Non-Small Cell Lung Cancer. Clin Cancer Res 26, 1162, doi:10.1158/1078-0432.CCR-19-1376 (2020).
  52. Sinha, A., Hussain, A., Ignatchenko, V. et al. N-Glycoproteomics of Patient-Derived Xenografts: A Strategy to Discover Tumor-Associated Proteins in High-Grade Serous Ovarian Cancer. Cell Syst 8, 345, doi:10.1016/j.cels.2019.03.011 (2019).
  53. Stewart, E. L., Mascaux, C., Pham, N. A. et al. Clinical Utility of Patient-Derived Xenografts to Determine Biomarkers of Prognosis and Map Resistance Pathways in EGFR-Mutant Lung Adenocarcinoma. J Clin Oncol 33, 2472, doi:10.1200/JCO.2014.60.1492 (2015).
  54. Stewart, J. M., Shaw, P. A., Gedye, C. et al. Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells. Proc Natl Acad Sci U S A 108, 6468, doi:10.1073/pnas.1005529108 (2011).
  55. Tiriac, H., Belleau, P., Engle, D. D. et al. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer. Cancer Discov 8, 1112, doi:10.1158/2159-8290.CD-18-0349 (2018).
  56. Wang, D., Pham, N. A., Tong, J. et al. Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors. Int J Cancer 140, 662, doi:10.1002/ijc.30472 (2017).
  57. Wang, D., Pham, N. A., Freeman, T. M. et al. Somatic Alteration Burden Involving Non-Cancer Genes Predicts Prognosis in Early-Stage Non-Small Cell Lung Cancer. Cancers (Basel) 11, doi:10.3390/cancers11071009 (2019).
  58. Wei, Y., Tong, J., Taylor, P. et al. Primary tumor xenografts of human lung adeno and squamous cell carcinoma express distinct proteomic signatures. J Proteome Res 10, 161, doi:10.1021/pr100491e (2011).
  59. Wu, L., Allo, G., John, T. et al. Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma. Clin Cancer Res 23, 1060, doi:10.1158/1078-0432.CCR-16-0844 (2017).
  60. Yoshihito Kano, T. G., Christopher Marshall, Nikolina Radulovich, Betty Poon, Jonathan St-Germain, Jonathan Cook, Ivette Valencia-Sama, Benjamin Grant, Silvia Herrera, Jinmin Miao, Brian Raught, Meredith Irwin, Jeffrey Lee, Jen Jen Yeh, Zhong-Yin Zhang, Ming-Sound Tsao, Mitsuhiko Ikura, and Michael Ohh. Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of Switch I and II conformation. Nature Communications (2018).
  61. Zhang, W., Wei, Y., Ignatchenko, V. et al. Proteomic profiles of human lung adeno and squamous cell carcinoma using super-SILAC and label-free quantification approaches. Proteomics 14, 795, doi:10.1002/pmic.201300382 (2014).

Our Team

Scientific Director
  • icon of personDr. Ming Tsao
Scientific Advisory Committee
  • icon of personDr. David Hedley
  • icon of personDr. Mathieu Lupien
  • icon of personDr. David Cescon
  • icon of personDr. Brad Wouters
  • icon of personDr. Laurie Ailles
  • icon of personDr. Catherine O'Brien
  • icon of personDr. Geoffrey Liu
  • icon of personDr. Trevor Pugh
  • icon of personDr. Robert Rottapel
Scientific Managers
  • icon of personDr. Nhu-An Pham (PDX Core)
  • icon of personDr. Nikolina Radulovich (PDO Core)
Supporting UHN Facilities
  • icon of buildingAnimal Resources Centre
  • icon of buildingBiospecimen Sciences Program
  • icon of buildingPM Genomics Centre
  • icon of buildingBioinformatics Core
  • icon of buildingDDP-AMPL Biomarker Lab
  • icon of buildingAOMF
  • icon of buildingCommercialization

Contact Us

Princess Margaret Living Biobank

The PMLB Core is located at:

Princess Margaret Cancer Research Tower
101 College St.
Toronto, Ontario
M5G 1L7

Contact
Email: pmlb@uhnresearch.ca

Image credit: UHN's Research Strategy team