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You are here: Home / Faculty / Dr. Marianne Sadar, PhD / Research Interests

Research Interests

  • Prostate cancer

  • Drug Development

  • Androgen Receptor

Dr. Sadar’s research accomplishments and experience over 22 years is essentially entirely focused on the development of therapeutics for prostate cancer. In 1999, Dr. Sadar discovered a novel drug target for prostate cancer. She then partnered with a chemist, Dr. Andersen, to screen drugs against this target, and discovered a clinical candidate of this drug. Dr. Sadar Founded a biotech company in 2009, called ESSA Pharma Inc,  to develop the drug for testing in clinical trials. This was successful and First-in-human clinical trials are currently active at 4 sites in USA and 1 site in Canada Clinical/Trials.gov Identifier: NCT02606123. Only one in a thousand drugs that show promise in laboratory studies and animal models ever reaches human testing. Dr. Sadar’s drug is the first drug in clinical trials that binds to an intrinsically disordered protein region and a first in class drug to the N-terminus of the androgen receptor. The work is precedent in the entire field of steroid hormone receptors, with no other small molecule inhibitor reported to bind to the N-terminus of any other steroid hormone receptor (Andersen et al Cancer Cell 2010; Myung et al JCI 2013). Validation of the novelty of her drug was provided by the USAN council and her drug was given a new stem class “-aniten” and the generic name “ralaniten”. In 2016, Dr. Sadar developed the first imaging agent to detect androgen receptor and its active splice variants in prostate cancer (Imamura et al JCI Insight. 2016). Dr. Sadar has served in numerous leadership roles internationally and is the Y2017 Chair of the USA Army’s Department of Defence’s Programmatic Panel for their Prostate Cancer Research Program. She is the first Canadian to serve in this position. She was the President of the Society of Basic Urologic Research (USA) and a board member of education, research, and scientific advisory committees and boards for American and Canadian non-profit societies. Of note is that Dr. Sadar was recently appointed to the Board of Trustees for Canada’s National Museum of Science and Technology by the Minister of Heritage. Dr. Sadar has served on over 50 grant panels including 5 years on the NIH study session for Drug Discovery & Molecular  Pharmacology. Her research has gained considerable media attention over the years with many interviews on radio, newspapers, television, and on the internet. Her research has also received awards such as the USA SWIU/SBUR Award for Excellence in Urologic Research, Simon Fraser University’s Outstanding Alumni Award for Academic Achievements, and the Terry Fox Young Investigator Award. Dr. Sadar has trained 40 students and 18 fellows of which many have gone onto successful medical or scientific careers. 

 

 

Selected Publications

74 total publications 1991-2017 | 4,814 total citations | H-index 34 | i10-index 58 tracked by Google Scholar as of Dec. 1, 2017

Leung JK and Sadar MD. Non-genomic actions of the androgen receptor in prostate cancer. Frontiers in Endocrinology. 2017 Jan 17;8:2. doi: 10.3389/fendo.2017.00002. eCollection 2017. PMID: 28144231

Banuelos CA, Tavakoli I, Tien AH, Caley DP, Mawji NR, Li Z, Wang J, Yang YC, Imamura Y, Yan L, Wen JG, Andersen RJ, Sadar MD. Sintokamide A is a Novel Antagonist of Androgen Receptor that Uniquely Binds Activation Function-1 in its Amino-Terminal Domain. Journal of Biological Chemistry. 2016 Oct 14;291(42):22231-22243. Epub 2016 Aug 30. PMID: 27576691

Obst JK and Sadar MD. Directing abiraterone metabolism: balancing the scales between clinical relevance and experimental observation. Translational Cancer Research. 2016 Jul 22. doi: 10.21037/tcr.2016.07.35.

Imamura Y, Tien AH, Pan J, Leung JK, Banuelos CA, Jian K, Wang J, Mawji NR, Fernandez JG, Lin KS, Andersen RJ, and Sadar MD. An imaging agent to detect androgen receptor and its active splice variants in prostate cancer. Journal of Clinical Investigation Insight. 2016 Jul 21;1(11). pii: e87850. PMID: 27525313

Antonarakis ES, Chandhasin C, Osbourne E, Luo J, Sadar MD, Perabo F. Targeting the N-terminal domain of the androgen receptor: a new approach for the treatment of advanced prostate cancer. The Oncologist. 2016 Dec;21(12):1427-1435. Epub 2016 Sep 14. PMID: 27628492

Imamura Y and Sadar MD. Androgen Receptor targeted therapies in Castration-Resistant Prostate Cancer; bench to clinic. International Journal of Urology. 2016 Aug;23(8):654-65. doi: 10.1111/iju.13137. Epub 2016 Jun 14. PMID: 27302572

Yang YC, Banuelos CA, Mawji NR, Wang J, Kato M, Haile S, McEwan IJ, Plymate S, Sadar MD. Targeting androgen receptor activation function-1 with EPI to overcome resistance mechanisms in castration-resistant prostate cancer. Clinical Cancer Research. 2016 Sep 1;22(17):4466-77. doi: 10.1158/1078-0432.CCR-15-2901. Epub 2016 May 2. PMID: 27140928

Kato M, Banuelos CA, Imamura Y, Leung JK, Caley DP, Wang J, Mawji NR, Sadar MD. Co-targeting Androgen Receptor Splice Variants and mTOR signaling pathway for the Treatment of Castration-Resistant Prostate Cancer. Clinical Cancer Research. 2016 Jun 1;22(11):2744-54. doi: 10.1158/1078-0432.CCR-15-2119. Epub 2015 Dec 28. PMID: 26712685

Banuelos CA, Lal A, Tien AH, Shah N, Yang YC, Mawji NR, Meimetis LG, Park J, Kunzhong J, Andersen RJ, Sadar MD. Characterization of niphatenones that inhibit androgen receptor N-terminal domain. PLoS One. 2014 Sep 30;9(9):e107991. doi: 10.1371/journal.pone.0107991. eCollection 2014. PMID: 25268119

Myung JK, Banuelos CA, Fernandez JG, Mawji NR, wang J, Tien AH, Yang YC, Tavakoli I, Haile S, Watt K, McEwan IJ, Pymate S, Andersen RJ, Sadar MD. An androgen receptor N-terminal domain antagonist for treating prostate cancer. Journal of Clinical Investigation. 2013 Jul;123(7):2948-60. doi: 10.1172/JCI66398. Epub 2013 Jun 3. PMID: 23722902

Meimetis LG, Williams DR, Mawji NR, Banuelos CA, Lal A, Park JJ, Tien AH, Fernandez JG, de Voogd NJ, Sadar MD, Andersen RJ. Niphatenones, Glycerol Ethers from the Sponge Niphates digitalis Block Androgen Receptor Transcriptional Activity in Prostate Cancer Cells: Structure Elucidation, Synthesis and Biological Activity. Journal of Medicinal Chemistry. 2012 Jan 12;55(1):503-14. doi: 10.1021/jm2014056. Epub 2011 Dec 28. PMID: 22148427

Romanuik TL, Wang G, Morozova O, Delaney A, Marra MA, Sadar MD. LNCaP Atlas: gene expression associated with in vivo progression to castration-recurrent prostate cancer. BMC Medical Genomics. 2010 Sep 24;3:43. doi: 10.1186/1755-8794-3-43. PMID: 20868494

 Andersen RJ, Mawji NR, Wang J, Wang G, Haile S, Myung JK, Watt K, Tam T, Yang YC, Banuelos AC, Williams DE, McEwan IJ, Wang YZ, Sadar MD. Regression of castrate-recurrent prostate cancer by a small molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell. 2010 Jun 15;17(6):535-46. doi: 10.1016/j.ccr.2010.04.027. PMID: 20541699

Quayle SN, Mawji NR, Wang J, Sadar MD. Androgen receptor decoy molecules block the growth of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2007 Jan 23;104(4):1331-6. Epub 2007 Jan 16. PMID: 17227854

Le L Chi K, Tylesley S, Flibotte S, Diamond DL, Kuzyk MA, Sadar MD. Identification of serum amyloid A as a biomarker to distinguish prostate cancer patients with bone lesions. Clinical Chemistry. 2005 Apr;51(4):695-707. Epub 2005 Feb 3. PMID: 1569532

Sobel RE, Sadar MD. Cell lines used in prostate cancer research: a compendium of old and new lines--part 2. Journal of Urology. 2005 Feb;173(2):360-72. PMID: 15643173

Sobel RE, Sadar MD. Cell lines used in prostate cancer research: a compendium of old and new lines--part 1. Journal of Urology. 2005 Feb;173(2):342-59. PMID: 15643172

Blaszczyk N, Masri BA, Mawji NR, Ueda T, McAlinden G, Duncan CP, Bruchovsky N, Schweikert HU, Schnabel D, Jones EC Sadar MD. Osteoblast-derived factors induce androgen-independent proliferation and expression of prostate-specific antigen in human prostate cancer cells. Clinical Cancer Research. 2004 Mar 1;10(5):1860-9. PMID: 15014041

Ueda T, Mawji NR, Bruchovsky N, Sadar MDLigand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells. Journal of Biological Chemistry. 2002 Oct 11;277(41):38087-94. Epub 2002 Aug 5. PMID: 12163482

Ueda T, Bruchovsky N, Sadar MD. Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. Journal of Biological Chemistry. 2002 Mar 1;277(9):7076-85. Epub 2001 Dec 19. PMID: 11751884

Sadar MD, Hussain M, Bruchovsky N. Prostate Cancer: Molecular Biology of Early Progression to Androgen Independence. Endocrine-Related Cancer. 1999 Dec;6(4):487-502. PMID: 10730903

Sadar MD. Androgen-independent induction of PSA gene expression via cross-talk between the androgen receptor and PKA signal transduction pathways. Journal of Biological Chemistry. 1999 Mar 19;274(12):7777-83. PMID: 10075669

 

 

Marianne Sadar's Complete Publication List with links to selected papers.

 

Patents:

Sadar MD and Imamura Y. Wee1 and EPI combo. Filing date: May 9, 2017. ESSA-026/00US.

Sadar MD, Mawji NR, OBst JK, Andersen RJ, Williams DE, Kunzhoung J. Compounds and methods for treating drug-resistant androgen receptor mediated cancers. U.S. Application No. 62/385648. Filing date: September 9, 2016. ESSA-022/00US.

Sadar MD and Leung JK. Compound combinations and methods for treating androgen receptor mediated cancers. Filing date: February 28, 2017. ESSA-025/00US.

Sadar MD and Mawji NR. Androgen receptor activators. Filing date: September 20, 2016.

Andersen RJ, Jian K, Mawji NR, Banuelos CA, Wang J, Yang YC, Sadar MD. Bisphenol derivatives and their use as androgen receptor activity modulators. U.S. Provisional Patent Application No. 62/323196. Filing date: April 15, 2016.

Sadar MD, Kato M, Mawji NR, Wang J. Co-targeting mTOR and the androgen receptor N-terminal domain for prostate cancer. U.S. Provisional Patent Application No. 62/213506. Filing date: September 2, 2015.

Sadar MD, Mawji NR, Banuelos CA, Andersen RJ, Kunzhong J, Bisphenol Ether Derivatives and methods for using the same. U.S. Provisional Patent Application No. 62/131969. Filing date: March 12, 2015.

Andersen RJ, Fernandez JG, Jian K, Sadar MD, Mawji NR, Banuelos CA. Heterocyclic Compounds for Cancer Imaging and Treatment and Metehods for Their Use. U.S. Provisional Patent Application No. 62/102719. Filing date: January 13, 2015.

Sadar MD, Leung J. Compositions and methods for treatment of prostate cancer. U.S. Provisional Appliccation No. 62/130696. Filing date: March 10, 2015.

Andersen RJ, Fernandez JG, Jian K, Sadar MD, Mawji NR, Banuelos CA. Heterocyclic Compounds for Cancer Imaging and Treatment and Methods for Their Use. U.S. Provisional Patent Application No. 62/102719. Filing date: January 13, 2015.

Sadar MD, Mawji NR, Wang J, Imamura Y, Tien A, Andersen RJ, Fernandez JG, Garcia J, Kunzhong J. Halogenated Compounds for Cancer Imaging and Treatment and Methods for Their Use. U.S. Application No. 14/481727. Filing date: September 9, 2014.

Yan L, Andersen RJ, Sadar MD, Mawji NR, Banuelos CA. Androgen Receptor Modulators and Methods for Their Use. U.S. Application No. 62/005714. [PCT/US15/33385] Filing date: May 30, 2014.

Andersen RJ, Fernandez JG, Sadar MD, Banuelos CA, Mawji N, Wang J. Fluoro-Cchloro Bisphenol Ether Compounds and Methods for Their Use. U.S. Provisional Patent Application No. 61/890670. Filing date: October 14, 2013.

Sadar MD, Andersen RJ, Fernandez JG, Yapp DT, Lin KS, Benard F, Tien A. 18F Compounds for Cancer Imaging and Method for Their Use. U.S. Provisional Patent Application No. 61/890679. [PCT/US2012/051923] Filing date: August 22, 2012.

Andersen RJ, Fernandez JG, Garcia J, Kunzhong J, Sadar MD, Mawji NR, Banuelos CA, Wang J, Imamura Y. I Compounds for Cancer Imaging and Methods for Their Use. U.S. Provisional Application No. 61/875556. Filing date: September 9, 2013.

Sadar MD, Mawji NR, Banuelos CA, Andersen RJ, Williams DE. Axamide-3 and Related compounds for Treatment of Cancer. Provisional Patent Application No. U.S. 61/868365. Filing date: August 21, 2013. U.S. Provisional Patent Application No. 61/693693. Filing date: August 27, 2012.

Andersen RJ, Fernandez JG, Sadar MD. Bisphenol Ether Compounds with Novel Bridging Groups and Methods for Their Use. U.S. Provisional Patent Application No. 61/868365. Filing date: July 3, 2013.

Andersen RJ, Sadar MD, Fernandez JG, Mawji NR, Wang J, Banuelos CA. Ester Derivatives of Androgen Receptor Modulators and Methods for Their Use. U.S. Application No. 14/274528. Filing date: May 9, 2014.

Andersen RJ, Sadar MD. Aziridine Bisphenol Ethers and Related compounds and Methods for Their Use. U.S. Application No. 13/863849. Filing date: April 16, 2013.

Andersen RJ, Fernandez JG, Sadar MD, Mawji NR, Banuelos CA, Wang J. Fluorinated Bisphenol Ether Compounds and Methods for Their Use. U.S. Application No. 13/588922. [PCT/US2012/051481] Filing date: August 17, 2012.

Andersen RJ, Fernandez JG, Sadar MD, Mawji NR, Banuelos CA, Wang J. Dibenzylphenyl Compounds and Methods for Their Use. PCT/US2012/033957. Filing date: April 17, 2012.

Andersen RJ, Fernandez JG, Sadar MD, Mawji NR, Banuelos CA, Wang J. Fluorene-9-Bisphenol Compounds and Methods for Their Use. PCT/US2012/033959. Filing date: April 17, 2012.

Andersen RJ, Fernandez JG, Sadar MD, Mawji NR, Banuelos CA, Wang J. Bisphenol Compounds and Methods for Their Use. U.S. Application No. 14/110615. [PCT/US2012/032584] Filing date: April 6, 2012.

Jones S, An J, Sadar MD, Mawji NR, Zoubeidi A. Compositions and methods for treatment of prostate cancer. Filing date: September 7, 2012.

Sadar MD, Mawji NR, Banuelos CA, Andersen RJ, Fernandez JG. Bisphenol Derivatives and Their Use as Androgen Receptor Activity Modulators. U.S. Application No. 13/520729. [PCT/CA2011/000019] Filing date: January 6, 2011.

Sadar MD, Mawji NR, Banuelos CA, Andersen RJ, Fernandez JG. Bisphenol Derivative Therapeuticsc and Methods for Their Use. U.S. Application No. 13/520731. [PCT/CA2011/000021] Filing date: January 6, 2011.

Sadar MD, Combination therapy uses for certain androgen receptor blocking compounds. U.S. Provisional patent application Filed at the USPTO in September, 2010.

Sadar MD, Mawji NR, Banuelos CA, Andersen RJ, Garcia Fernandez J. Achiral Group Containing Bisphenol Derivative Therapeutics and Methods for their Use. Full PCT Application No. P110100034. Filing date: January 6, 2010.

Lam S, Yee J, Kuzyk M, Sin D, Sadar MD, Tammemagi CM. Methods for detecting lung cancer and monitoring treatment response. U.S. Application No. US12/743042. [PCT/CA2008/002070]. Filing date: November 24, 2008.

Sadar MD, Mawji NR, Wang J, Andersen RJ, Williams DR, LeBlanc M. Diglycidic Ether Derivative Therapeutics and Methods for Their Use. U.S. Application No. 12/999037. [PCT/CA2009/000902] Filing date: April 19, 2013.

Sadar MD, Mawji NR, Wang J, Andersen RJ, Williams DE, LeBlanc M, Yan LP. Small Molecular Inhibitors of N-Terminus Activation of the Androgen Receptor. U.S. Application No. 12/999035. [PCT/CA2009/001173] Filing date: August 24, 2009.

Sadar MD, Quayle SN, Hare H. Biomarkers and Methods for the Prognosis of Androgen-Independent Prostate Cancer. U.S. Provisional patent application Filed at the USPTO in March 2009.

Sadar MD, Bruchovsky N, Gout PW, Snoek R, Mawji NR. Peptide inhibitors of androgen-independent activation of androgen receptor. PCT/CA1999/000604. Filing date: June 30, 1999.

 

Page last modified Dec 01, 2017