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Northwestern University Feinberg School of Medicine
Department of Urology
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Prostate Cancer

Studying molecular, genetic and environmental contributors to prostate cancer to improve prostate cancer prevention, diagnosis and treatment.  

 Sarki Abdulkadir Lab

Studying the mechanisms of prostate cancer initiation, progression and recurrence and strategies to therapeutically target these processes

Research Description

Our laboratory focuses on understanding the molecular mechanisms that drive prostate cancer initiation, progression and recurrence with the ultimate goal of developing therapeutic strategies that target these processes. Our approach includes the genomic analysis of human tumors, cell culture studies and the use of genetically engineered mouse models. We have a strong interest in genomics and gene regulation, oncogenic kinases as potential molecular therapeutic targets and the use of in vivo lineage tracing to define the fates of specific cell populations in tumorigenesis.

Specific projects include:

The role of the oncogenic serine/threonine kinase PIM1 in prostate cancer - PIM1 is coexpressed with c-MYC and dramatically enhances c-MYC-driven prostate tumorigenesis in a kinase-dependent manner. Notably, PIM1 is induced in tumors by hypoxia, radiation and treatment with docetaxel, a common but largely ineffective option for patients with advanced castration-resistant prostate cancer. PIM1 induction by hypoxia/radiation/docetaxel promotes prostate cancer cell survival and therapeutic resistance. Therefore, PIM1 may represent a valuable therapeutic target in prostate cancer. We are using new mouse models of prostate cancer for testing the efficacy of novel PIM1 kinase inhibitors in treating prostate cancer and reversing therapeutic resistance. We have also identified novel candidate PIM1-interacting proteins in prostate epithelial cells. Among the proteins identified are a MYC transcriptional cofactor and a prostate stem cell marker/regulator. We are investigating how PIM1 promotes prostate tumorigenesis by phosphorylating these substrates involved in regulating MYC transcriptional activity and stem cell function.

Cellular and molecular determinants of prostate cancer recurrence - A major clinical problem in prostate cancer is that of tumor recurrence following initial apparently successful therapy. Recurrent tumors may arise from a small number of "cancer stem-like cells" that survive the initial therapeutic intervention and have the capacity to regenerate the tumor. We are using lineage tracing to examine the competence of specific prostate epithelial cell types to regenerate tumors following therapy in mice.

Targeting lethal prostate cancer – We are using our mouse model of lethal prostate cancer based on alterations in Myc, Pten and Tp53 to develop new targeted therapies. One current project involves the targeting of EphB4 receptor tyrosine kinase using an antagonist as a therapeutic strategy.

For more information, see Dr. Abdulkadir's faculty profile.

Publications

Sagar V, Vatapalli R, Lysy B, Pamarthy S, Anker JF, Rodriguez Y, Han H, Unno K, Stadler WM, Catalona WJ, Hussain M, Gill PS, Abdulkadir SA. EPHB4 inhibition activates ER stress to promote immunogenic cell death of prostate cancer cells. Cell Death and Disease. November 2019.

Han H, Jain AD, Truica MI, Izquierdo-Ferrer J, Anker JF, Lysy B, Sagar V, Luan Y, Chalmers ZR, Unno K, Mok H, Vatapalli R, Yoo YA, Rodriguez Y, Kandela I, Parker JB, Chakravarti D, Mishra RK, Schiltz GE, Abdulkadir SA. Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. Cancer Cell.  November 2019.

Njoroge RN, Vatapalli RJ, Abdulkadir SA. Organoids increase the predictive value of in vitro cancer chemoprevention studies for in vivo outcome. Frontiers in Oncology. January 2019.

 


See Dr. Abdulkadir's publications in PubMed.

 

Contact Us

Dr. Abdulkadir
Lab Telephone: 312-503-5031

 William Catalona Lab

Investigating genetic insights into the causes of prostate cancer and its possible treatments and cures

Research Description

For more than 25 years, Dr. Catalona’s research has contributed significantly to the areas of early detection, treatment and cures for prostate cancer. His research aims to provide genetic insights into the causes of prostate cancer. He has discovered several new regions of the human genome statistically associated with prostate cancer. His current research is studying genetic variants associated with aggressive disease in men enrolled in active surveillance protocols from around the country.

Dr. Catalona is also the PI of the Specialized Programs of Research Excellence (SPORE) in prostate cancer; one of only eight in the country. This is a multidisciplinary NCI project in prostate cancer translational research.  The overall goals of the SPORE are to investigate: cell and molecular biology of prostate cancer, prevention and risk factors in prostate cancer development; innovative therapeutics and rehabilitation; and quality of life and outcomes research. 

Publications

Lopes Vendrami C, McCarthy RJ, Chatterjee A, Casalino D, Schaeffer EM, Catalona WJ, Miller FH. The Utility of Prostate Specific Antigen Density, Prostate Health Index and Prostate Health Index Density in Predicting Positive Prostate Biopsy Outcome is Dependent on the Prostate Biopsy Methods. Urology. July 2019.

Giri VN, Knudsen KE, Kelly WK, Abida W, Andriole GL, Bangma CH, Bekelman JE, Benson MC, Blanco A, Burnett A, Catalona WJ, et al.  Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017. Journal of Clinical Oncology. February 2018.

Loeb S, Shin SS, Broyles DL, Wei JT, Sanda, M, Klee G, Partin AW, Sokoll L, Chan DW, Bangma CH, van Schaik RHN, Slawin KM, Marks LS, Catalona WJ. Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer. BJU International. July 2017.

 Qi Cao Lab

Identifying novel molecular therapeutic targets for advanced prostate cancer

Research Description

Polycomb group (PcG) proteins help to regulate gene expression in normal cells. Research shows that this family of proteins is associated with prostate cancer initiation, disease progression and metastasis. The Cao lab is particularly interested EZH2, a specific protein within the PcG family. The lab’s previous research identified EZH2 as a biomarker for aggressive breast cancer as well as characterized EZH2 as an oncogene which represses multiple tumor suppressors in breast and prostate cancer.  This work has demonstrated EZH2 as a valuable therapeutic target in cancer, and several pharmaceutical companies are developing EZH2- or BMI1- specific inhibitors for cancer therapy.

The Cao lab is also working to identify miRNAs targeting Polycomb group proteins and other oncogenes in cancer. Using bioinformatics, they identified the miRNAs, which target EZH2, EED, BMI1, and RING1B, in cancer. This research suggested that genomic loss of miR-101 leads to the overexpression of EZH2 in cancer. In addition, PRC2 complex represses a set of miRNAs, including miR-181a,b, miR-200b,c and miR-203, which, in turn, repress BMI1 and RING1B. In advanced cancer, loss or epigenetic repression of these miRNAs leads to upregulation of PRC1 proteins BMI1 and RING1B, epithelial-mesenchymal transition regulators ZEB1 and ZEB2, and histone methyltransferase MMSET. This study suggests these miRNAs may serves as therapeutic targets for advanced cancer patients.

For more information, see the faculty profile of Qi Cao, PhD.

Select Publications

Zhu S, Zhao D, Li C, Li Q, Jiang W, Liu Q, Wang R, Fazli L, Li Y, Zhang L, Yi Y, Meng Q, Wang W, Wang G, Zhang M, Zu X, Zhao W, Deng T, Yu J, Dong X, Chen K, Cao Q. BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Oncogene. 2020 Jan.

Liu, Q., Wang, G., Li, Q., Jiang, W., Kim, J. S., Wang, R., Zhu, S., Wang, X., Yan, L., Yi, Y., Zhang, L., Meng, Q., Li, C., Zhao, D., Qiao, Y., Li, Y., Gursel, D. B., Chinnaiyan, A. M., Chen, K. & Cao, Q. Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer.  Int J Cancer. 2019 Jan 10.

Zhu, S., Zhao, D., Yan, L., Jiang, W., Kim, J. S., Gu, B., Liu, Q., Wang, R., Xia, B., Zhao, J. C., Song, G., Mi, W., Wang, R. F., Shi, X., Lam, H. M., Dong, X., Yu, J., Chen, K. & Cao, Q. BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nat Commun. 2018 Feb 5;9(1):500.

 Adam Murphy Lab

Studying the biologic and environmental sources of health disparities in prostate cancer

Research Description

Dr. Murphy's group investigates etiologies and modifiable risk factors for health disparities in prostate cancer. They study the biological and environmental mediators of serum vitamin D deficiency and prostate cancer risk. Dr. Murphy's group also assesses the role of HIV infection on the incidence and treatment of prostate cancer. Finally, they evaluate barriers of prostate cancer screening for African American men using community-based participatory research methods.

For more information, see the faculty profile of Adam B Murphy, MD, MBA.

 

Publications

Murphy AB, Carbunaru S, Nettey OS, Gornbein C, Macias V, Sharifi R, Kittles RA, Yang X, Kajdacsy-Balla A, Gann P, Dixon MA. A 17-Gene Panel Genomic Prostate Score Has Similar Predictive Accuracy for Adverse Pathology at Radical Prostatectomy in African American and European American Men. Urology. 2020 Jan.

Carbunaru S, Nettey OS, Gogana P, Helenowski IB, Jovanovic B, Ruden M, Hollowell CMP, Sharifi R, Kittles RA, Schaeffer E, Gann P, Murphy AB. A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort. BMC Urology. November 2019.

Murphy AB, Nyame YA, Batai K, Kalu R, Khan A, Gogana P, Dixon M, Macias V, Kajdacsy-Balla A, Hollowell CMP, Catalona WJ, Kittles R. Does prostate volume correlate with Vitamin D deficiency among men undergoing prostate biopsy? Prostate Cancer and Prostatic Disease. October 2017.

For a complete list of publications, refer to Northwestern Scholars.

 Ashley Ross Lab

Developing novel diagnostic and therapeutic strategies for prostate cancer

Research Description

Ashley Ross MD, PhD, is an active clinician and surgeon scientist with expertise in prostate cancer, genomics, immunology, targeted therapies and clinical trials.  His research is focused on improving the diagnosis and treatment of clinically significant prostate cancer, including the development of prognostic and predictive biomarkers in prostate cancer and the initiation of clinical trials. 

Dr. Ross is an expert in the design and conduct of early phase clinical trials. He has conducted clinical trials utilizing novel therapeutic approaches to lethal prostate cancer including use of immunotherapies, targeted oncogenic pathway inhibitors, and the use of more potent androgen deprivation.

In this video, Dr. Ross describes the biomarker-driven clinical trials that are showing promise for prostate cancer and other future research directions in the field. Watch here>>

For more information, see the faculty profile of Ashley E Ross, MD, PhD.

Select Publications

Ross AE, Hurley PJ, Tran PT, Rowe SP, Benzon B, Neal TO, Chapman C, Harb R, Milman Y, Trock BJ, Drake CG, Antonarakis ES. A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis. March 2020.

McKay RR, Ye H, Xie W, Lis R, Calagua C, Zhang Z, Trinh QD, Chang SL, Harshman LC, Ross AE, et al. Evaluation of intense androgen deprivation before prostatectomy: a randomized phase II trial of enzalutamide and leuprolide with or without abiraterone. J Clin Oncol. April 2019.

Ross AE, Hughes RM, Glavaris S, Ghabili K, He P, Anders NM, Harb R, Tosoian JJ, Marchionni L, Schaeffer EM, Partin AW, Allaf ME, Bivalacqua TJ, Chapman C, O'Neal T, DeMarzo AM, Hurley PJ, Rudek MA, Antonarakis ESPharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.  Oncotarget. October 2017.

View a full list of publications by Ashley Ross on PubMed

 

 Edward Schaeffer Lab

Concentrating on the prostate with an emphasis on diagnosis and treatment outcomes, the molecular biology of lethal prostate cancer and populations at risk for aggressive, lethal disease

Research Description

The laboratory of Edward Schaeffer, MD, PhD, conducts groundbreaking prostate cancer research focused on at-risk populations, diagnosis, treatment outcomes, and the molecular biology of lethal prostate cancer.  As Chair of the Department of Urology at Northwestern Medicine and Program Director of the Genitourinary Oncology Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Dr. Schaeffer is championing leading-edge explorations that are advancing scientific and clinical care pathways in prostate cancer.

Molecular biology of prostate development and prostatic disease: Dr. Schaeffer proposed the concept that the lineage of a prostate epithelial cell is established early, upon exposure to androgen, and that this lineage affects subsequent re-activation of embryonic growth pathways in pathologic prostatic conditions including BPH and prostate cancer.  This body of work has resulted in an international recognition as a prostate embryologist and established the paradigm of “lineage addiction” of the prostate epithelial cell to androgen signaling.  

Clinical and molecular biology of high risk prostate cancer: Dr. Schaeffer’s clinical and molecular work has brought international recognition to the previously under appreciated observation that aggressive (high risk), localized prostate cancer is frequently lethal and often undertreated. His research  on the clinical-biologic features of men with high risk disease and the molecular underpinnings driving prostate cancers defined a new subset of the particularly lethal cancer, outlined the molecular basis driving them and begun to lead clinical trials designed to improve the oncologic outcomes for these men.

The impact of race on the biology of prostate cancer: African American men with prostate cancer are twice as likely to develop metastasis and die of the disease than Caucasian men. Dr. Schaeffer’s work demonstrated a more aggressive biologic subset of cancers in African American men. His other discoveries include: (1) distinctive anatomic locations of African American tumors, (2) molecular expression signatures of African American cancers that demonstrate decreased reliance on androgen signaling, (3) novel solid tumor gene fusions and (4) divergent biomarkers panels signaling aggressive disease. 

In this video, Dr. Schaeffer shares some of the exciting developments underway at Northwestern to better understand racial disparities in prostate cancer. Watch to learn more>>

Tools to aid in clinical decision-making: One of the greatest challenges in prostate cancer management is identifying patients that will progress to advanced disease following treatment. The Schaeffer lab has developed and validated a genomic signature to predict response to anti-androgen therapies in order to guide treatment selection. The lab is currently refining this analysis to broaden our understanding of the molecular features of those who do and do not respond to treatment. In this video, he shares details about and future directions of this work. Watch to learn more>>

For more information, see the faculty profile of Edward Schaeffer, MD,PhD or lab website. 

Select Publications

Faisal FA, Murali S, Kaur H, Vidotto T, Guedes LB, Salles DC, Kothari V, Tosoian JJ, Han S, Hovelson DH, Hu K, Spratt DE, Baras AS, Tomlins SA, Schaeffer EM, Lotan TL. CDKN1B Deletions are Associated with Metastasis in African American Men with Clinically Localized, Surgically Treated Prostate Cancer. Clin Cancer Res. 2020 Jan 22.

Simons BW, Kothari V, Benzon B, Ghabili K, Hughes R, Zarif J, Ross AE, Hurley PJ, Schaeffer EM. A mouse model of prostate cancer bone metastasis in a syngeneic immunocompetent host. Oncotarget. 2019 Dec 3;10(64):6845-6854.

Spratt DE, Alshalalfa M, Fishbane N, Weiner AB, Mehra R, Mahal BA, Lehrer J, Liu Y, Zhao SG, Speers C, Morgan TM, Dicker AP, Freedland SJ, Karnes RJ, Weinmann S, Davicioni E, Ross AE, Den RB, Nguyen PL, Feng FY, Lotan TL, Chinnaiyan AM, Schaeffer EM. Transcriptomic Heterogeneity of Androgen Receptor Activity Defines a de novo low AR-Active Subclass in Treatment Naïve Primary Prostate Cancer.Clin Cancer Res. 2019 Nov 15;25(22):6721-6730.


Refer to PubMed for a full list of publications. 

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