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 350 publications, an h-index of 40 and 6,783 citations as of January 2020.
His scientific aptitude is reflected in his continuous governmental funding of his work since his appointment in 2007 and a large NIH award – a U01 on the “Molecular and cellular characterization of screen detected and lethal prostate cancers”
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. Ted 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. 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 over the last 10 years 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 has brought recognition to this key biologic and clinical issue in multiple ways. First he has completely re-defined the meaning of “high risk” localized prostate cancer with multiple (over 25) clinical translational publications. This work culminated in a new, refined definition of the disease that is now incorporated into the National Comprehensive Cancer Network Guidelines. Secondly, 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.
This work has further refined our definition of this disease and is now being utilized by large cooperative oncology groups (ECOG -Eastern Cooperative Oncology Group and SWOG Southwest Oncology Group, for example) as a platform to design large Phase II and Phase III national clinical trials. Lastly, these clinical genomic signatures of localized lethal prostate cancer have been the impetus for the initiation of clinical trials in this space. One such trial, initiated by Dr. Schaeffer and Dr. Ross, a former postdoctoral fellow, involved the discovery of an actionable non – androgen driven molecular pathway (hedgehog pathway) activated in lethal prostate cancers. They have taken this discovery to the clinics in the setting of an ongoing Phase 1 clinical trial.
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 on the clinical-biologic features of men with high risk disease and the molecular underpinnings driving prostate cancers with lethal potential has had a major impact on our understanding of the disease. His work has 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. 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. He has demonstrated a more aggressive biologic subset of cancers in African American men. Several of his team’s 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. His work has culminated with over 10 publications on this topic in the last several years including two publications in the Journal of Clinical Oncology. Furthermore, 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 — further affirming the significance of his discoveries. It has also resulted in further modifications to the National Prostate Cancer Management guidelines and heightened Dr. Schaeffer’s international reputation as an expert in prostate cancer management. The recent award of a large NIH U01 on the molecular and cellular characterization of prostate cancer in Caucasian and African American men additionally affirms his expertise in the molecular basis of prostate cancer.