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:5/27/2016)... ... ... Doctors in Italy, Japan, the UK and the US have reached some surprising ... its link to malignant mesothelioma. Surviving Mesothelioma has just posted the details of their ... , The studies analyzed for the new report included more than 3,447 cancer patients. ...
(Date:5/26/2016)... NEW YORK , May 26, 2016 ... announced today that it will be a featured presenter at ... 2016 in New York City at ... Denis Corin , Q BioMed Inc. CEO, is scheduled ... presentation will cover the company,s business strategy, recent developments and ...
(Date:5/25/2016)... ... May 25, 2016 , ... Lajollacooks4u has become a rising hotspot ... rated one of its top attractions. Fortune 500 companies, such as Illumina, Hewlett-Packard, ... unique and intimate team-building experience. , Each event kicks off with an olive oil ...
(Date:5/25/2016)... , ... May 25, 2016 , ... Scientists at the ... options being tried for mesothelioma may be hampering the research that could lead to ... Click here to read it now. , The team evaluated 98 ...
Breaking Biology Technology:
(Date:3/14/2016)... , Allemagne, March 14, 2016 ... ) - --> - Renvoi : image ... --> --> ... biométriques, fournit de nouveaux lecteurs d,empreintes digitales pour ... de DERMALOG sera utilisé pour produire des cartes ...
(Date:3/10/2016)... 10, 2016   Unisys Corporation (NYSE: UIS ... (CBP) is testing its biometric identity solution at the ... to help identify certain non-U.S. citizens leaving the country. ... designed to help determine the efficiency and accuracy of using ... and will run until May 2016. --> ...
(Date:3/8/2016)... March 8, 2016   Valencell , the ... announced it has secured $11M in Series D ... a new venture fund being launched by UAE-based ... from existing investors TDF Ventures and WSJ Joshua ... continue its triple-digit growth and accelerate its pioneering ...
Breaking Biology News(10 mins):