Major Research Areas
Molecular Pharmacology & Chemistry

Introduction

Recent data suggest that shedding of prostate cancer cells into blood occurs at an early stage of disease while the tumor is still confined to the prostate. We hypothesize that the extracellular actions of prostatic kallikreins and related proteases are involved in tissue remodeling that enhances prostate cancer progression and results in the loss of the basal cell layer, basal lamina integrity, and the frequent shedding of prostate cells into blood. It is therefore possible that selective, reliable, and early identification of men at high-risk for prostate cancer, before they develop frequent shedding of prostate cells into blood, may be a relevant target population for chemopreventive studies.

Approach

Over the past several years, we have developed fully standardized, highly reproducible, and robust real-time quantitative RT-PCR assays to measure PSA- and hK2-mRNA copy numbers as a means to detect circulating prostate cells (CPC) in blood.

Based on our recent data from an initial small-size preliminary evaluation of these assays, we now hypothesize that the vast majority of men with clinically significant localized prostate cancer may frequently shed circulating prostate/tumor cells in blood, in contrast to men who harbor indolent (insignificant) cancer, and men with no evidence of prostate cancer on biopsy who DO NOT (frequently) shed prostate/tumor cells in blood.

Objectives

Using contemporary criteria to select men for systematic prostate biopsies, we will investigate the diagnostic and prognostic utility of circulating prostate cells in prostate cancer using our quantitative RT-PCR assays targeting PSA- and hK2-mRNA. We will:

  1. Correlate the presence and quantity of target transcripts in blood from men found with prostate cancer compared with the men with no evidence of prostate cancer on prostate biopsies;
  2. Correlate the presence and quantity of target transcripts to the pathologic features that distinguish indolent from significant cancer;
  3. Assess whether the presence or quantity of circulating cell transcripts has significant association with advanced pathologic features at radical prostatectomy, as clinical evaluation often understages the pathologic extent of prostate cancer.

Collaborators

The following are collaborators from outside Memorial Sloan-Kettering:

  • Professor Kim Pettersson, PhD, and Professor Timo Lövgren, PhD, Chairman, Department of Biotechnology, University of Turku, Finland, who are involved in the development and design of highly sensitive disease markers, such as various forms of troponin for myocardial ischemia, osteocalcin for osteoporosis, PSA, and hK2 for prostate cancer. 
  • Hartwig Huland, MD, is Professor and Chairman of the Department of Urology at University Hospital, (UKE), Hamburg, Germany, and contributes a comprehensive biorepository with careful clinical follow up from about 1100 men referred to the Department of Urology at UKE, Hamburg, to undergo detailed biopsy-based clinical and pathologic evaluation. About 500 to 600 men are treated by radical prostatectomy annually.

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