Dr Fred Saad, MD FRCS

Full Professor and Chief of Urologic Oncology, CHUM;
Medical Director of Interdisciplinary Urologic Oncology Group, CHUM;
Department of Surgery/Faculty of Medicine;
Institut du cancer de Montréal/CRCHUM.

 

Key words: Urologic Oncology, Prostate cancer, Tissue bank, Prognostic biomarkers, Castrated-resistant prostate cancer, Personnalized medicine, NF-kB p65, IKKe, Microfluidic technologies, Tridimentionnal prostate cancer models

Contact :

fred.saad@umontreal.ca

Office: 514-890-8000 x.27466

1985  M.D., University of Montreal, Medicine

1990  Diploma, University of Montreal, Urology

1991  Fellow, University Laval, Urology Oncology

2007-present  University of Montreal Health Centers, Chairman, Division of Urology

2004-present  University of Montreal, Endowed Chair in prostate cancer Research

  • 2013-2016  (PI) Team grant, Movember GAP.
    “Unique TMAs project.”

  • 2013-2016  (PI) Team grant, Movember GAP.
    “Tissue biomarker project.”

  • 2012-2016  (PI) Terry Fox Research Institute.
    “The Canadian Prostate Cancer Biomarker Network.” 

  • 2015-2017  (co-PI) Continuum de recherche, Centre de Recherche du CHUM.
    “Vibrational Spectroscopy for Prostate Cancer Prognosis.”

  • 2015-2017  (co-PI) Movember discovery grant, Prostate Cancer Canada.
    “Adaptation of inelastic scattering detection technology for label-free molecular imaging to improve the reliability of prostatic biopsies.”             

  • 2015-2020  (co-PI) Team grant, Prostate Cancer Canada.
    “Development of a Targeted Oncolytic Virus Vaccine for the Treatment of Metastatic Prostate Cancer.”              

 

Awards and prizes

2005  University of Montreal Hospital Leadership and Outstanding achievement award

2010  CUASF Lecture: 2010 Annual CUA meeting (outstanding contribution to Canadian Urology)

2012  University of Montreal Department of Surgery senior mentor award

2013  Lifetime achievement award in research, CHUM Research Center/University of Montreal

 

Invited Lectures/professorships over 300 Lectures in over 30 countries and over 20 universities

 

Understand the mechanisms involved in the progression of prostate cancer

Development of tools for personnalized medicine in prostate cancer

Molecular prognostic markers for progression of prostate cancer

* One of the major challenge for the clinician in prostate cancer (PC) is to correctly identify patients with clinically insignificant cancer who can be managed with active surveillance, and avoid under-treating those with a more aggressive biological phenotype. It is clear that the development of new, more effective and specific biomarkers with increased sensitivity and specificity is urgently needed to enable us to identify individuals at increased risk of developing aggressive tumors.

 

* Homonal therapies and chemotherapies are commonly used alone or in combination for the treatment of advanced PC. Due to their associations with numerous adverse effects and risk of severe late toxicity, the judicial use of these therapies is critical. Therefore, the direct testing of patient tumor biopsies should allow for empirical evaluation of therapeutic responses to a wide variety of agents to support clinical decision-making. The combination of microfluidic technologies and ex vivo cultured micro-dissected tumors is a viable model to empirically predict treatment feedback in PC.

 

* We know that inflammation, in PC, can affect the tumor growth and how patients respond to treatment. We believe that early on in PC, a protein, called IKKe, does not help the cancer grow because hormones are present. However, during hormone therapy there is a shift in the biology of the cancer and IKKe becomes activated and eventually helps the cancer to spread and become resistant to therapy by affecting inflammation. We develop several projects to test these ideas.

 

* Our clinical research interests focus on the treatment of metastatic PCs via new therapeutic approaches including targeted treatments, combined treatments, vaccines (immunotherapy), and new forms of chemotherapies and gene therapies. We also have several projects on the prevention of metastase appearance in high-risk patients in addition to the biomarker projects to decide whether to treat newly diagnosed patients.

 

Current projets (techniques used):

* Define the prognostic value of biomarkers in prostate cancer by immunofluorescence. Fluorescent staining and signal quatification are performed using automated systems. The potential of each molecular biomarker is evaluated by correlation with clinical parameters and biochemical recurrence risk.

 

* Determine in vitro the effect of androgen receptor (AR) stimulation and IKKe-expression on prostate cancer cell proliferation and survival. We analyzed, using cell motility and proliferation assays, the effect of AR stimulation/inhibition on IKKe-expressing hormone-sensitive PC cells, the impact of exogenous AR expression on castrate-resistant PC cells and the role of IL-6 in PC cell survival without androgen. We are also conducting experiments to determine which mechanism is involved in PC cell proliferation/survival (cell death, senescence or cell cycle arrest). We perform a large mouse study using a sub-cutaneous PCa xenograft model to assess the role of AR in the control of IKKe over-expressing tumor development

 

* Determine the correlation between ex vivo and in vivo cultured prostate cancer tissue responses to hormone therapy and chemotherapy. In this project, we compare the response to treatment of micro-dissected xenograft tissues (ex vivo model) in microfluidic devices with matched mouse xenografts (in vivo model). We are following, on-chip and in mice, the impact of chemotherapies (cabazitaxel and docetaxel) and hormonal therapy (enzalutamide) on the survival and growth of hormone-sensitive and castrate-resistant PC xenografts.

 

* Evaluate the potential of microfluidic devices to empirically test patient response to different therapies. We are recruiting advanced castrate- and chemo-resistant PC patients treated at the CHUM CRPC clinic. We study the sensitivity of patient PC to varios treatments and the correlation between PC response/survival and inflammatory cytokine secretion using microfluidic devices. These results will be compared to the patient’s clinical evolution (i.e. survival as well as PSA, IL-6 and IL-8 serum levels) to evaluate the potential role of a microfluidic platform to predict patient response to secondary hormonal therapies and chemotherapies used in the treatment of metastatic castrate-resistant PC.

 

* We have always around 20 multi-center clinical trials (phase I, II and III). The CHUM has contributed significantly in the development of almost all new treatments emerged in the last 15 years to treat PC.
 

 

Post-docs

Abdul Lateef (lateefjh@gmail.com)
Amine Lounis (lounis.amine@hotmai.com)

Past (5 years)

Valérie Forrest
Mustapha Benaissa

 

PhD Students

Sylvie Clairefond (clairefond.sylvie@gmail.com)
Yannick Huon (yannick.huon@gmail.com)
Sophie Gilbert (sophiegilbe@gmail.com)

Past (5 years)

Ingrid Labouba
Philippe Gannon
Hervé Koumakpayi

 

MSc Student

Kayla Simeone (kayla.simeone@umontreal.ca)

Past (5 years)

Marc Olivier Bienz

 

Research Associates

Euridice Carmona (euricarmona@gmail.com)
Cécile Le Page (cecilelepage@yahoo.ca)
Benjamin Péant (peantb@yahoo.fr)
Véronique Ouellet (ouelletv@gmail.com)

 

Senior Research Assistant

Estelle Schmitt (estellem.schmitt@gmail.com)

 

Research Assistants

  1. Alexandria Aubourg (alexandria.aubourg.chum@ssss.gouv.ca)

  2. Chantale Auger (chantaleauger12@yahoo.com)

  3. Véronique Barrès (veronique.barres@gmail.com)

  4. Monique Bernard (monique.bernard@umontreal.ca)

  5. Renée Bernatchez (renee.bernatchez.chum@ssss.gouv.qc.ca)

  6. Christine Caron (caron_christine25@hotmail.com)

  7. Geneviève Cormier (genevievecormier@gmail.com)

  8. Manon de Ladurantaye (manon.deladurantaye.chum@ssss.gouv.qc.ca)

  9. Nathalie Delvoye (nathaliedelvoye@yahoo.ca)

  10. Gabriela Fragoso (fragosogabriela@yahoo.com)

  11. Doris Jiofack (risdoj@yahoo.fr)

  12. Jennifer Kendall-Dupont (jen.kendalldupont@gmail.com)

  13. Kim Leclerc-Desaulniers (kim.leclerc-desaulniers.chum@ssss.gouv.qc.ca

  14. Liliane Meunier (liliane.meunier@gmail.com)

  15. Adriana Orimoto (adriorimoto@gmail.com)

  16. Claudia Syed (claudia.syed@gmail.com)

  17. Teodora Yaneva (teoyan@gmail.com)

 

Administrative Assistants

Louise Champoux (louise.champoux3@sympatico.ca)
Mélanie Morin (melanie.morin.chum@ssss.gouv.qc.ca)

 

Scientific Writer

Jacqueline Chung (jwachung@gmail.com)

 

Bioinformatician

Nicolas Luc (nicol.luc@gmail.com)

  1. Peant, B., et al., IkappaB-Kinase-epsilon (IKKepsilon/IKKi/IkappaBKepsilon) expression and localization in prostate cancer tissues. Prostate, 2011. 71(10): p. 1131-8.

  2. Scher, H.I., et al., Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med, 2012. 367(13): p. 1187-97.

  3. Smith, M.R., et al., Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet, 2012. 379(9810): p. 39-46.

  4. Gannon, P.O., et al., Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer. Eur J Cancer, 2013. 49(10): p. 2441-8.

  5. Ryan, C.J., et al., Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med, 2013. 368(2): p. 138-48.

  6. Beer, T.M., et al., Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med, 2014. 371(5): p. 424-33.

  7. Ryan, C.J., et al., Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol, 2015. 16(2): p. 152-60.

  8. Labouba, I., et al., Potential Cross-Talk between Alternative and Classical NF-kappaB Pathways in Prostate Cancer Tissues as Measured by a Multi-Staining Immunofluorescence Co-Localization Assay. PLoS One, 2015. 10(7): p. e0131024.

  9. Blume-Jensen, P., et al., Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clin Cancer Res, 2015. 21(11): p. 2591-600.

  10. Astolfi, M., et al., Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy. Lab Chip, 2016. 16(2): p. 312-25.