Navigation Links
New Study Raises Questions About Prostate Cancer Therapies Targeting Insulin-Like Growth Factor Receptor

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

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


Dean Forbes

(206) 667-2896

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:
(Date:11/24/2015)... AVIV, Israel , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: ... held on December 29, 2015 at 11:00 a.m. Israel ... Co., Electra Tower, 98 Yigal Allon Street, 36 th Floor, ... election of Eric Paneth and Izhak Tamir to ... and Rami Skaliter as external directors; , approval of an amendment ...
(Date:11/24/2015)... SAN FRANCISCO , Nov. 24, 2015 /PRNewswire/ ... today announced that Emily Leproust, Ph.D., Twist Bioscience ... Piper Jaffray Healthcare Conference on December 1, 2015 ... Palace Hotel in New York City. ... . Twist Bioscience is on ...
(Date:11/24/2015)... Switzerland (PRWEB) , ... November 24, 2015 , ... InSphero ... organotypic 3D cell culture models, has promoted Melanie Aregger to serve as Chief Operating ... Ms. Aregger served on the management team and was promoted to Head ...
(Date:11/24/2015)... Nov. 24, 2015 /CNW Telbec/ - ProMetic Life Sciences Inc. ... that Mr. Pierre Laurin , President and Chief Executive ... the upcoming Piper Jaffray 27 th Annual Healthcare Conference ... December 1-2, 2015. st , at 8.50am ... meetings throughout the day. The presentation will be available live ...
Breaking Biology Technology:
(Date:11/17/2015)... Paris from 17 th until 19 ... from 17 th until 19 th November 2015. ... invented the first combined scanner in the world which scans ... now two different scanners were required: one for passports and ... the same surface. This innovation is an ideal solution for ...
(Date:11/12/2015)... , Nov. 12, 2015  A golden retriever ... Duchenne muscular dystrophy (DMD) has provided a new lead ... Children,s Hospital, the Broad Institute of MIT and Harvard ... Brazil . Cell, pinpoints ... dogs "escape" the disease,s effects. The Boston Children,s lab ...
(Date:11/10/2015)... 10, 2015 About signature ... helps to identify and verify the identity of ... as the secure and accurate method of authentication ... particular individual because each individual,s signature is highly ... when dynamic signature of an individual is compared ...
Breaking Biology News(10 mins):