Navigation Links
New Study Raises Questions About Prostate Cancer Therapies Targeting Insulin-Like Growth Factor Receptor
Date:5/1/2008

SEATTLE, May 1 /PRNewswire/ -- Therapies under development to treat prostate cancer by inhibiting the ability of insulin-like growth factor (IGF-1) to activate its target receptor could have unexpected results, especially if a major tumor suppressor gene -- p53 -- is already compromised, according to new research by investigators at Fred Hutchinson Cancer Research Center.

IGF-1 is a polypeptide hormone that can influence growth, differentiation and survival of cells expressing the type 1 receptor (IGF-1R). Past clinical, epidemiological and experimental studies have strongly implicated IGF-1 as a contributing factor in the natural history of prostate cancer. However, very little has been done to prove absolutely that the expression or activation of the IGF-1 signaling pathway at physiologically relevant levels is sufficient to cause a healthy prostate cell to become a cancer cell.

Norman Greenberg, Ph.D., and colleagues conducted a pair of experiments by manipulating gene expression directly in the epithelial compartment of the mouse prostate gland to better understand the role of IGF-1R. In contrast to studies that correlated elevated levels of IGF-1 with the risk of developing prostate cancer, Greenberg's research showed that eliminating IGF-1R expression in an otherwise normal mouse prostate caused the cells to proliferate and become hyperplastic. Although persistent loss of IGF-1R expression ultimately induced cell stasis and death, both of these processes are regulated by the tumor suppressor gene p53 that is commonly mutated in human prostate cancers. Hence the researchers hypothesized that tumors with compromised p53 might not respond predictably to therapies targeting IGF1 signaling.

To test their reasoning they conducted a second experiment by crossing mice carrying the prostate-specific IGF-1R knockout alleles with transgenic mice that develop spontaneous prostate cancer when p53 and select other genes are compromised. The results were as predicted: Prostate epithelial-specific deletion of IGF-1R facilitated the emergence of aggressive prostate cancer in the genetically-engineered tumor prone mice.

Published in the May 1 edition of Cancer Research, the study supports a critical role for IGF-1R signaling in prostate tumor development and identifies an important IGF-1R-dependent growth control mechanism, according to the authors. Title of the paper is "Conditional deletion of insulin-like growth factor-1 receptor in prostate epithelium."

"If our predictions hold true, tumor cells with intact p53 may show the best response to therapy targeting the IGF-1R signal, however when p53 is not functioning normally, response to this therapy may not be as expected," said Greenberg, the study's corresponding author and a member of the Hutchinson Center's Clinical Research Division.

Greenberg's message to clinicians who administer IGF-R1 therapy: "We're all hoping for good results but let's proceed with caution."

A search of the database for clinical trials registered with the National Cancer Institute found 18 trials in process that use therapies to inhibit IGF-R1. None of them include a tumor's p53 status as a criterion for recruiting research participants, said Greenberg.

In addition to lead author Brent Sutherland, Ph. D., of the Hutchinson Center, contributing research also came from scientists at Baylor College of Medicine in Houston, Texas, the Center for Cancer and Stem Cell Biology at Texas A&M University and the Institut National de la Sante et de la Recherche Medicale in Paris, France.

The study was funded by the National Cancer Institute, the Prostate Cancer Foundation and Phi Beta Psi.

Note to reporters/editors: To obtain a copy of the study, please contact Dean Forbes, 206-667-2896 or dforbes@fhcrc.org

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.

CONTACT

Dean Forbes

(206) 667-2896

dforbes@fhcrc.org


'/>"/>
SOURCE Fred Hutchinson Cancer Research Center
Copyright©2008 PR Newswire.
All rights reserved

Related biology technology :

1. Statement from Lighthouse International About the Study on Gene Therapy Concerning Lebers Congenital Amaurosis
2. Kaiser Permanente Study Finds Diabetes Doubling Before Motherhood
3. Pharmasset Adds Two Cohorts to R7128 Hepatitis C Study
4. Dosing for RVX-208 Phase 1a Clinical Study Completed
5. Study Suggests GAMMAGARD LIQUID May Target the Primary Pathway Involved in Alzheimers Disease
6. DermTech Study on Melanoma Molecular Diagnostic to Be Presented at AACR
7. ANX-530 Demonstrates Equivalent Pharmacokinetics to Navelbine(R) in a Registrational Bioequivalence Clinical Study
8. GeneNews reports positive results from validation study of colorectal cancer biomarkers in late-breaking abstract at AACR
9. Spectrals EAA(TM) to be used in Phase III study for a sepsis anti-endotoxin therapy
10. ThromboGenics Completes Patient Enrolment of MITI IV Trial, a Phase II Study Evaluating the Safety and Preliminary Efficacy of Microplasmin in the Treatment of Acute Stroke
11. CyberKnife Prostate Cancer Planning Study Published in Leading Radiation Oncology Journal
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... Rolf K. Hoffmann, former ... of the University of North Carolina Kenan-Flagler Business School effective June ... UNC Kenan-Flagler, with a focus on the school’s international efforts, leading classes and ...
(Date:6/24/2016)... Brooklyn, NY (PRWEB) , ... June 24, 2016 , ... ... 15mm, machines such as the Cary 5000 and the 6000i models are higher end ... height is the height of the spectrophotometer’s light beam from the bottom of the ...
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... , June, 23, 2016  The Biodesign Challenge (BDC), ... new ways to harness living systems and biotechnology, announced ... (MoMA) in New York City . ... participating students, showcased projects at MoMA,s Celeste Bartos Theater ... Antonelli , MoMA,s senior curator of architecture and design, ...
Breaking Biology Technology:
(Date:6/7/2016)...  Syngrafii Inc. and San Antonio Credit Union ... integrating Syngrafii,s patented LongPen™ eSignature "Wet" solution into ... result in greater convenience for SACU members and ... existing document workflow and compliance requirements. ... Highlights: ...
(Date:6/2/2016)... , June 2, 2016 Perimeter ... Platforms, Unmanned Systems, Physical Infrastructure, Support & Other Service  ... visiongain offers comprehensive analysis of the global ... market will generate revenues of $17.98 billion in 2016. ... DVTEL Inc, a leader in software and hardware technologies ...
(Date:5/16/2016)...   EyeLock LLC , a market leader of ... an IoT Center of Excellence in Austin, ... of embedded iris biometric applications. EyeLock,s iris ... security with unmatched biometric accuracy, making it the most ... EyeLock,s platform uses video technology to deliver a fast ...
Breaking Biology News(10 mins):