|
Study raises questions about prostate cancer therapies targeting IGF-1
May 01, 2008SEATTLE - 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.
Fred Hutchinson Cancer Research Center
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.
Fred Hutchinson Cancer Research Center
Prostate Cancer News and Current Prostate Cancer Events RSSFirst worldwide analysis of cancer survival finds wide variation between countries
Cancer survival varies widely between countries according to a worldwide study published online today in Lancet Oncology.* More than 100 investigators contributed to the study.
Possible link found between x-rays and prostate cancer
Researchers at The University of Nottingham have shown an association between certain past diagnostic radiation procedures and an increased risk of young-onset prostate cancer - a rare form of prostate cancer which affects about 10 per cent of all men diagnosed with the disease.
Prostate cancer vaccines more effective with hormone therapy
Among patients with castration-resistant prostate cancer, the addition of hormone therapy following vaccine treatment improved overall survival compared with either treatment alone or when the vaccine followed hormone treatment, according to recent data published in the July 15 Clinical Cancer Research, a journal of the American Association for Cancer Research.
Counting tumor cells in blood predicts treatment benefit in prostate cancer
Counting the number of tumor cells circulating in the bloodstream of patients with castration-resistant prostate cancer can accurately predict how well they are responding to treatment, new results show.
Elevated biomarkers predict risk for prostate cancer recurrence
A simple blood test screening for a panel of biomarkers can accurately predict whether a patient who has had prostate cancer surgery will have a recurrence or spread of the disease.
Researchers identify promising cancer drug target in prostate tumors
Scientists at Dana-Farber Cancer Institute report they have blocked the development of prostate tumors in cancer-prone mice by knocking out a molecular unit they describe as a "powerhouse" that drives runaway cell growth.
Certain anticancer agents could be harmful to patients with heart disease
A set of promising new anticancer agents could have unforeseen risks in individuals with heart disease, suggests research at Washington University School of Medicine in St. Louis.
Risk of death after cancer diagnosis; shift in stage of breast cancer diagnosis
Cancer patients with low socioeconomic status (SES) have more advanced cancers at diagnosis, receive less aggressive treatment, and have a higher risk of dying in the five years following cancer diagnosis, according to a new study.
UT Southwestern urologists identify seven biomarkers that may help pinpoint prostate cancer recurrence
A simple blood test may help doctors better predict whether prostate cancer will recur or spread in patients who have undergone surgery for the disease, UT Southwestern Medical Center researchers have found.
Radiation therapy prolongs life in men with recurrent prostate cancer
Men whose tumors recur after prostate cancer surgery are three times more likely to survive their disease long term if they undergo radiotherapy within two years of the recurrence.
More Prostate Cancer News Articles
 | Dr. Patrick Walsh's Guide to Surviving Prostate Cancer, Second Edition by Patrick C. Walsh, Janet Farrar Worthington |
 | The Vitamin D Cure by James Dowd, Diane Stafford |
 | You Can Beat Prostate Cancer by Robert J. Marckini |
 | A Primer on Prostate Cancer: The Empowered Patient's Guide by Stephen Strum, Donna L. Pogliano |
 | Prostate Health in 90 Days by Larry Clapp |
 | Eat to Beat Prostate Cancer Cookbook by David Ricketts |
 | Prostate Cancer for Dummies by Paul H. Lange, Christine Adamec, Christine Adamec |
 | Prostate And Cancer: A Family Guide To Diagnosis, Treatment And Survival (3rd Edition) by Sheldon Marks |
 | Dr. Patrick Walsh's Guide to Surviving Prostate Cancer by Patrick C. Walsh, Janet Farrar Worthington |
 | The Natural Prostate Cure by Roger Mason |
| © 2008 BrightSurf.com |