Navigation Links
How some prostate tumors resist treatment -- and how it might be fixed
Date:3/18/2013

LA JOLLA, Calif., March 18, 2013 Hormonal therapies can help control advanced prostate cancer for a time. However, for most men, at some point their prostate cancer eventually stops responding to further hormonal treatment. This stage of the disease is called androgen-insensitive or castration-resistant prostate cancer. In a study published March 18 in Cancer Cell, a team led by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) found a mechanism at play in androgen-insensitive cells that enables them to survive treatment. They discovered that a protein called Siah2 keeps a portion of androgen receptors constantly active in these prostate cancer cells. Androgen receptorssensors that receive and respond to the hormone androgenplay a critical role in prostate cancer development and progression.

Based on this new information, Siah2 could make a promising biomarker for tracking a prostate cancer patient's response to therapy. Inhibiting Siah2's interaction with the androgen receptor complex might also provide a new method for re-sensitizing castration-resistant prostate tumors to hormone therapy.

Siah2 removes the brake on androgen receptors

"Prostate tumors become castration-resistant by using diverse ways to modify androgen receptor to become constantly active. In this study, we demonstrate how this happens through a previously unknown mechanism orchestrated by Siah2. Surprisingly, it turns out that only a fraction of all androgen receptors are altered in castration-resistant tumors," said Ze'ev Ronai, Ph.D., associate director of Sanford-Burnham's National Cancer Institute-designated Cancer Center, scientific director of the Institute's La Jolla campus, and senior author of the study.

Normally, androgen receptors are kept in check by an inhibitor called NCOR1. This study revealed that, in castration-resistant prostate tumors, Siah2 tags the NCRO1-androgen receptor complex for degradation. That removes the brake, allowing the recycling of inactive androgen receptor to active status. As a result, prostate cancer cells produce more active androgen receptors, which render them resistant to hormone therapy.

Clinical relevance

Ronai and colleagues wondered if Siah2 plays the same role in real-life castration-resistant prostate cancer as they had observed in the lab. Using samples provided by collaborators at the Vancouver Prostate Centre at the University of British Columbia, the team determined that human castration-resistant prostate tumors have abnormally high levels of Siah2 and select androgen receptor targets. This finding underscores the clinical significance of the castration-resistance mechanism they uncovered.

Ronai and his team also looked at what happens when they inhibit Siah2. To do this, they used three different animal models. In each case, inhibiting Siah2 restored prostate tumors' sensitivity to hormone therapy. With Siah2 out of the picture, prostate tumors regressed during hormone therapy.

"We see Siah2 not only as a biomarkera way to track the development and progression of castration-resistancebut also as a potential therapeutic target for prostate cancer," explained Jianfei Qi, Ph.D., staff scientist in Ronai's lab and first author of the paper.


'/>"/>
Contact: Heather Buschman
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert  

Related medicine news :

1. New drug prevents spread of human prostate cancer cells
2. 2 genetic deletions in human genome linked to the development of aggressive prostate cancer
3. Intensity Modulated Radiation Therapy optimal for localized prostate cancer
4. Study examines adverse effects among different radiation therapies for prostate cancer
5. Study Casts Doubt on Value of Pricey Prostate Cancer Therapy
6. Warren Buffett Has Early Stage Prostate Cancer
7. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
8. PSA screening to detect prostate cancer can be beneficial to younger and at-risk men
9. Mayo Clinic researchers discover biomarkers for prostate cancer detection, recurrence
10. Quality of care, other issues may cause worse results in black prostate cancer surgery patients
11. Higher hospital volume more important than surgeon experience in outcome of prostate cancer surgery
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
How some prostate tumors resist treatment -- and how it might be fixed
(Date:2/27/2017)... ... February 27, 2017 , ... Texas ... week. In addition, Discount Power's RCE (Residential Customer Equivalent) count exceeds 150,000. ... The company had 800 customers and 2,250 RCEs at the time of acquisition. ...
(Date:2/27/2017)... Francisco, CA (PRWEB) , ... February 27, 2017 ... ... clinic serving San Francisco and environs, is proud to announce an upgrade to ... information on the upgraded Yelp page on topics as diverse as Platelet Rich ...
(Date:2/26/2017)... ... February 26, 2017 , ... Today, A' Design Awards ... of International Social Design Awards. , The 7th A' Social Design Award ... and Institutions worldwide with realized projects and conceptual works. , The first phase ...
(Date:2/26/2017)... York, New York (PRWEB) , ... February 26, ... ... luxury baby products for wholesale distribution in North America, today announced it would ... online sites. The company, which prides itself on crafting quality and unique baby ...
(Date:2/26/2017)... ... 2017 , ... ODH, Inc.™ announced today it will exhibit and speak ... City Hotel in Arlington, VA. ODH’s director of medical strategy, Candace Saldarini, M.D., will ... Medicaid population health management. , ODH will also have an exhibit booth where attendees ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... , Feb. 24, 2017 Juan Monteverde ... Associates PC , a boutique securities firm headquartered at ... City , announces that a class action lawsuit ... Massachusetts  against Inotek Pharmaceuticals Corporation (NASDAQ:  ITEK)("Inotek" ... Company,s securities between July 23, 2015 and December 30, 2016, ...
(Date:2/24/2017)... MELBOURNE , Australien, 24. Februar 2017 /PRNewswire/ ... innovatives, diversifiziertes Unternehmen des Gesundheitsbereiches, ist erfreut, für ... Vergleich mit dem entsprechenden Vorjahreszeitraum exzellente Ergebnisse vorlegen ... BioMedical und Aktualisierung zum Wachstum" finden Sie ... Gewinn nach Steuern 2,12 Millionen USD (Dez. 2015: ...
(Date:2/24/2017)... NEW YORK , Feb. 23, 2017  This ... US$ Thousand by the following Products: ... analyzed in the report include Pharmaceuticals, and Agrochemicals. The ... Japan , Europe , ... provided for the period 2015 through 2022. Also, a ...
Breaking Medicine Technology: