Dr. Edward Schaeffer’s research activities concentrate on the prostate with an emphasis on the diagnosis, treatment outcomes, the molecular biology of lethal prostate cancer and populations at risk for aggressive, lethal disease. His discoveries in this field have resulted in defining manuscripts that have altered the basic scientific understanding of prostate cancer and have changed clinical care pathways multiple times. Dr. Schaeffer’s CV provides many examples of these accomplishments: He has 381 publications, an h-index of 41 and 7,170 citations as of May 2020.
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’s most basic research has focused on striking similarities between the invasive, growth charged phases of prostatic development and prostatic diseases. With this work, 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 work established the paradigm of “lineage addiction” of the prostate epithelial cell to androgen signaling. It has served as the basis for continuous funding in his lab since 2007, including the prestigious Howard Hughes Medical Institute Early Careers Award. Dr. Schaeffer remains the only Urologist to ever have received this highly competitive grant.
Clinical and Molecular Biology of High Risk Prostate Cancer. The prostate cancer landscape has increasingly emphasized the over treatment of men with non-lethal forms of prostate cancer. While true, 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. Dr. Schaeffer re-defined the meaning of “high risk” localized prostate cancer. This work resulted in a new, refined definition of the disease that is now incorporated into the National Comprehensive Cancer Network Guidelines. Additionally, Dr. Schaeffer has moved the definition of this type of prostate cancer into the “molecular era” with several first in field manuscripts on the clinical – genomics of lethal prostate cancer.
A multi-institutional study led by Dr. Schaeffer sought to characterize androgen receptor activity (AR-A) in localized prostate cancer, and understand its molecular and clinical implications. The study, published in Clinical Cancer Research, is the largest genomic analysis of prostate cancer to date, encompassing nearly 20,000 patients with localized prostate cancer. This large-scale genomic analysis of localized prostate cancer is notable as it helps us understand the molecular machinery driving the most aggressive cases, and simultaneously exposed novel pharmacologic vulnerabilities.
In sum, Dr. Schaeffer’s work has defined a new subset of the particularly lethal cancer and outlined the molecular basis driving these cancers. Future research aims to investigate effective therapeutic modalities and develop robust biomarkers for treatment intensification and improved clinical outcomes.
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 as Caucasian men. The reasons underlying this had been poorly understood; however, Dr. Schaeffer’s work on this topic has revealed multiple first-in-field discoveries on biologic differences in prostate cancers in men of African descent. Dr. Schaeffer’s team has described distinct anatomic differences in prostate cancers occurring in African Americans, including molecular expression signatures that demonstrate decreased reliance on androgen signaling, novel solid tumor gene fusions, and divergent biomarker panels signaling aggressive disease. He has shown that African American men stage-for-stage and grade-for-grade have cancers with more aggressive biology and is currently working to identify additional outliers in African American prostate cancers to explain this increased risk for aggressive disease.
In 2013, Dr. Schaeffer’s work on this topic was acknowledged by the American Society of Clinical Oncology’s as a Clinical Cancer Advance of 2013. It has also resulted in further modifications to the National Prostate Cancer Management guidelines and was the basis for a NIH U01 grant to study the molecular and cellular characterization of prostate cancer in Caucasian and African American men.
Optimizing Prostate Cancer Treatment. 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. The implications of this research is the development of a genomic test to assist in the utilization of adjuvant or multimodal therapies to reduce the rate of disease progression and prostate cancer mortality.
PET/MRI for the Detection and Staging of Prostate Cancer: Northwestern Memorial Hospital has the Chicago area’s first combined positron emission tomography (PET) and magnetic resonance imaging (MRI) scanner. Dr. Schaeffer has initiated a clinical trial at Northwestern to test the efficacy of PET/MRI for the staging of newly diagnosed prostate cancer. He hypothesizes that the synergism of PET and MRI can offer vastly superior anatomic detail and biologic data that are extremely valuable in advanced evaluation of prostate cancer, particularly with respect to surgical and radiation planning as well as in assessing therapy response.
Modeling Treatment Response with Organoids: To identify which chemotherapies and hormonal therapies could effectively treat aggressive prostate tumors, Dr. Schaeffer is partnering with Sarki Abdulkadir, MD, PhD, to grow prostate cancer tissue from men with localized disease. These prostate “organoids” appear very similar to the prostate cancers they are derived from and have the potential to model individual patient sensitivities to new drug therapies. Ultimately, this research could result in customized treatment plans for patients with aggressive prostate cancers.
Developing Nano-Scale Therapeutics for Prostate Cancer: The direct delivery of therapeutic drugs to a specific tissue has not been successfully applied to prostate cancer. Dr. Schaeffer is collaborating with Milan Mrksich, PhD, to synthesize and characterize a library of novel targeted therapeutic candidates, based on the ‘megamolecule’ platform, to deliver the drug directly to specific prostate cancer cells. This method will reduce toxicity on non-cancer cells while effectively targeting prostate cancer cells.