Navigation Links
Study raises questions about prostate cancer therapies targeting IGF-1
Date:4/30/2008

SEATTLE 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, Greenbergs 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 studys corresponding author and a member of the Hutchinson Centers Clinical Research Division.

Greenbergs message to clinicians who administer IGF-R1 therapy: Were all hoping for good results but lets 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 tumors p53 status as a criterion for recruiting research participants, said Greenberg.


'/>"/>

Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
Source:Eurekalert

Related medicine news :

1. Children More Vulnerable to Harmful Effects of Lead at Age 6 Than as Toddlers, Says New Study
2. Flip Flops, Mulch and No Coat: Study Identifies Surprising Barriers to Outdoor Activity for Kids in Child-Care Centers
3. Penn study finds elderly heart patients with ICD devices live longer after heart failure
4. Physical activity, healthy eating and BMI not linked in older teens: study
5. Salk study links diabetes and Alzheimers disease
6. U of M study: Online intervention paramount for reducing HIV in high-risk population
7. Study Reveals Women Feeling Growing Financial Pressures on Family Life
8. Experimental Blood Substitutes Unsafe, Study Finds
9. Spinal cord injury research hampered by animal models, says new study
10. Study: Casual Video Games Demonstrate Ability to Relieve Stress, Improve Mood: Potential Clinical Significance Highlighted
11. Kaiser Permanente study finds diabetes doubling before motherhood
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... A revolution is underway. ... ambulance transport experience for the millions of people who require these medical transport ... taxi industry through the use of technology. Now, SmartEMS has put forth an ...
(Date:6/26/2016)... ... , ... Pixel Film Studios Released ProSlice Levels, a Media Slicing Effect ... a whole new perspective by using the title layers in ProSlice Levels to ... ProSlice Levels contains over 30 Different presets to choose from. FCPX users ...
(Date:6/25/2016)... ... June 25, 2016 , ... Experts from ... at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the Hynes Convention Center ... care topics including advance care planning, healthcare costs and patient and family engagement. ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency ... named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. ... Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director ...
(Date:6/25/2016)... ... , ... Conventional wisdom preaches the benefits of moderation, whether it’s a matter ... bar too high can result in disappointment, perhaps even self-loathing. However, those who set ... , Research from PsychTests.com reveals that behind the tendency to set low ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on ... today announced that patient enrollment in its ongoing ... Duchenne) has exceeded 50% of its 24-patient target. ... in the third quarter of 2016, and to ...
(Date:6/23/2016)... , , , WHEN: ... , , , , LOCATION: , , , Online, with ... , EXPERT PANELISTS:  , , , Frost & Sullivan,s Global Vice ... Senior Industry Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... industry is witnessing an exceptional era. Several new demand spaces, such ...
(Date:6/23/2016)... Revolutionary technology includes multi-speaker listening to conquer ... in advanced audiology and hearing aid technology, has today ... world,s first internet connected hearing aid that opens up ...      (Photo: http://photos.prnewswire.com/prnh/20160622/382240 ) , ... , TwinLink™ - the first dual communication ...
Breaking Medicine Technology: