Publications

Publications

Metastasis as a therapeutic target in prostate cancer: a conceptual framework

By:
Contributors: Andries Zijlstra Research Group, Katie Hebron, John D. Lewis Research Group, David Bond, PhD, Konstantin Stoletov, PhD, Srijan Raha
Am J Clin Exp Urol. 2014 Apr;2(1):45-56.

Abstract

Metastasis is the main cause of prostate cancer-associated deaths. While significant progerss has been made in the treatment of primary tumors, efficent therapies that target the metastatic spread of prostate cancer are far from clinical reality. To efficiently treat cancer we need be able to impede its spread. Unfortunately, the majority of current therapeutics approved to treat metastatic cancer were originally selected based on their ability to inhibit primary tumor growth. This inherent flaw precluded these therapies from efficiently targeting the development of secondary metastatic lesions, a process that is distinct from that of primary tumor progression. In this review we will summarize the conceptual, cellular and molecular targets that should be considered to design effective anti-metastatic therapies.

 

PubMed

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Dr. Nawaid Usmani and team receive funding for their PRIME study!

The PRIME Study – Prevention and Intervention for MEtabolic syndrome:

Androgen deprivation therapy (ADT), and newer manipulations of androgen receptor signaling have improved outcomes for advanced prostate cancer (PCa) patients.  The toxicities of ADT are many, including an increased risk of developing metabolic syndrome (MS; defined as at least 3 of: hyperglycemia; abdominal obesity; hypertriglyceridemia; reduced HDL cholesterol; and/or hypertension). MS is associated with an increased risk of diabetes, cardiovascular disease mortality, stroke mortality, and all-cause mortality.  The prevalence of MS in men receiving ADT is at least 50% and contributes to decreased quality of life and increased non-cancer-related mortality.  Metformin holds promise as a countermeasure to MS development, and also has been shown to suppress PCa growth in pre-clinical models.

We hypothesize that the addition of metformin to ADT will reduce the rates of MS in men with advanced PCa, diminishing important toxicities of a therapy universally used in advanced disease.

We propose a double-blind, randomized phase III study of metformin or placebo in men with PCa starting intermittent ADT. The primary endpoint is the difference in MS rates at 1 year.  Other aims include evaluation of the influence of metformin on: individual MS components at additional time points; mean serum insulin levels and measures of insulin resistance; weight and quality of life.

A finding that metformin reduces MS incidence and/or has other benefits would change practice, as it would provide a practical and inexpensive strategy to reduce toxicity of an intervention employed in most men with advanced PCa.

- Catalina Vasquez