The Department of Urology has ambitious goals for our bench to bedside prostate cancer research. Most new drugs take 10 years and $1 billion to get to market; the objective of the Tewari Laboratory and our Richard LeFrak Young Investigators is to achieve a turn out time of five years from Research/Discovery to Benefit.
Personalized treatment is the focus of research being directed by Kamlesh Yadav, MTech, PhD, Assistant Professor, Urology, Icahn School of Medicine at Mount Sinai. His research comprises of tumor modeling and genomic susceptibility analysis. The goal of tumor modeling is to identify drug-sensitivity and minimize resistance to treatment. To accomplish this, patient tumors are treated with various drugs in the labs in order to determine the most responsive sensitivities. Tumors are sequenced in order to identify the genomic alterations that drive tumorigenesis and then predict the best drug combinations. The team has sequenced more than 20 treatment naïve tumors to date. Another aspect of Dr. Yadav’s research is exploring if drugs already approved by the Food and Drug Administration for different disease states can be used to treat end stage prostate cancer. Dr. Yadav is looking at the collective cell expression profile of prostate cancer and utilizing a computational program to match drugs that antagonize the tumor profile. We are partnering closely with the Department of Genetics and Genomic Sciences on this effort. Currently five drugs are being investigated at the cellular level, and we have two lead compounds at various stages of pre-clinical trials in mice.
Our other research projects include:
Molecular Mechanisms and Functional Validation
The research goal for Sujit S. Nair, PhD, is to understand molecular mechanisms and functional validation of transcriptional, epigenetic and genome surveillance roles of chromatin remodelers, immunomodulators, histone modifying enzymes, lnCRNA, and miRNA in prostate cancer. He is pursuing studies on understanding tumor immunology and the impact on prostate cancer progression and on reciprocal crosstalk between diabetes and prostate cancer, using a combined genomic and proteomic approach.
Prognostic Role of Hexim1
Dr. Nair is also working on a collaborative initiative between Ash Tewari, MBBS, MCh, FRCS, and Manya Mascareno, PhD, SUNY College Downstate Medical Center, to validate the prognostic role of Hexim1 in prostate cancer. One of the major objectives of the study is to evaluate levels of Tyrosine phosphorylated Hexim1 in tissue microarray with clinical outcome data and determine if Hexim1 is a good biomarker to distinguish between indolent and aggressive disease, independent of clinicopathological variables and current biomarkers.
Prostate Cancer Heterogeneity
Shalini Singh, PhD, Instructor, Urology, Icahn School of Medicine, is analyzing prostate cancer heterogeneity using next generation sequencing approaches. Her focus is on using cutting-edge single cell genomics and transcriptomic approaches to develop simple, non-invasive diagnostic tests for prostate cancer. She leads research projects focused on understanding spatial and temporal heterogeneity; understanding disparities in prostate cancer incidence and death rates between black and white men; and understanding the role of tumor microenvironment in tumor growth.
Vaccine Before Surgery
The Department of Urology is working with the Division of Hematology and Medical Oncology on the viability of a vaccine to be administered before surgery that would boost a patient’s immune system to halt tumor growth. The study is the first of its kind to use the RNA molecule Hiltonol (polyCLC). We are working collaboratively with other leading research institutions, including Cold Spring Harbor Laboratory, Massachusetts Institute of Technology, Harvard University, Dana-Farber Cancer Institute, Cornell University, The Broad Institute, and Rockefeller University, to carry out advanced genetic studies on prostate cancer tissue and develop new techniques for diagnosing and treating prostate cancers.
Active surveillance for prostate cancer is rarely a treatment of choice, with only 10 percent of eligible, low-risk prostate cancer patients in the United States opting for it. Additionally, there is evidence that approximately 50 percent of men on active surveillance discontinue the protocol within five years for no clear reasons. To date, no study formally defines or measures patient factors or preferences leading to their decisions to discontinue active surveillance to receive curative treatment. To address this gap, Dr. Tewari and Nihal Mohamed, PhD, are conducting research among patients on active surveillance within the Mount Sinai Health System. The study examines the acceptability and feasibility of an innovative, care planning intervention to increase adherence to active surveillance, improve patients’ quality of life and psychosocial outcomes (e.g., psychological distress, decisional regret, uncertainty, fear of cancer progression, and satisfaction with care and communication), and address patients’ unmet informational and supportive care needs.
Gold Nanoparticle Directed Focal Therapy
Mount Sinai is embarking on a gold nanoparticle directed focal therapy trial, the first one of its kind. In preclinical studies, gold nanoparticles (AuroLase Therapy) have been shown to provide highly selective and rapid tissue destruction with minimal damage to surrounding tissue, enabling a potentially curative treatment of tumors with minimum toxicity. Gold nanoparticles are able to actively target and conform to areas of high vascularity associated with abnormal tissue growth within the prostate. Ardeshir Rastinehad, DO, is national co-principal investigator of this study in partnership with Steven Canfield, MD, at the University of Texas Medical School at Houston and Joshua Stern, MD, of the Albert Einstein School of Medicine and Montefiore Medical Center in New York. The objective of the trial is to determine the efficacy of using MRI/US fusion imaging technology to direct focal ablation of prostate tumors/tissue using laser activated gold nanoparticle directed ablation in human subjects while assessing adverse effects attributable to the treatment. Another presumed outcome is a lower incidence of erectile dysfunction and urinary incontinence compared to other types of prostate cancer treatment.