Navigation Links
Genetic approach provides new insight into trastuzumab resistance in breast cancer
Date:10/15/2007

A new study provides important insight into the mechanisms involved in resistance to treatment of breast cancer patients with trastuzumab (Herceptin). The research, published by Cell Press in the October issue of the journal Cancer Cell, identifies markers that may help to identify patients who are unlikely to respond to trastuzumab treatment and provides a potential strategy for treating these patients.

Trastuzumab is an antibody used as a therapy for patients whose breast cancers produce excess amounts of the protein HER2. However, almost half of these breast cancer patients are nonresponsive to trastuzumab therapy or become resistant during treatment. To better understand the antitumor activity of trastuzumab, Dr. Rene Bernards from The Netherlands Cancer Institute and his colleagues used a large-scale genome-wide RNA interference screen to search for genes involved in trastuzumab resistance in breast cancer.

The researchers identified only the tumor suppressor PTEN as a modulator of trastuzumab sensitivity in a breast cancer cell line. Earlier findings had associated PTEN with resistance to trastuzumab-based therapy, and loss of PTEN is known to result in hyperactivation of the PI3K pathway. Abnormal activation of this cell survival signaling pathway has been identified in many primary breast cancers. Hyperactivation of the PI3K pathway also can be caused by activating mutations of the PIK3CA gene.

This finding, along with the high frequency of PIK3CA activating mutations in breast cancer, led us to investigate whether PI3K pathway activity, as assessed by cancer-associated activating mutations (of PIK3CA) or altered levels of PTEN, was able to predict trastuzumab resistance in the clinic, explains Dr. Bernards. This combined analysis identified twice as many patients at increased risk for disease progression as would analyzing PTEN alone and proved to be statistically significant as a biomarker for prognosis after trastuzumab therapy, indicating that assessment of PTEN expression together with PIK3CA mutation is required for optimal prediction of disease progression after trastuzumab therapy for breast cancer.

Importantly, this study also illustrates the power of in vitro RNAi screens combined with confirmation on patient samples to identify biomarkers useful for predicting treatment response in the clinic, says Dr. Bernards. It is too early to use these biomarkers; further validation studies are required before they can be used in the clinic. Nevertheless, it is likely that these findings will lead to a better understanding of resistance mechanisms and how to circumvent them as well as more reliable identification of the most effective treatment for individual patients.


'/>"/>
Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Genetic Dentistry: Your Dentist may be able to grow you a new set of Teeth.
2. Crowning glory of 2000!!! Cracking of the genetic code is top of tops
3. Genetic influence in menopause
4. Genetic differences found between Male and Female brains
5. Genetic Breakthrough in Common Eye Problem
6. Inflammatory bowel disease linked to genetic abnormality
7. Genetic Code Of C.difficile Cracked
8. Genetics and cholesterol levels
9. Genetics helps in attacking cancer
10. DNA biochip for genetic screening
11. Genetic disorder related with sleep patterns
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/16/2017)... NY (PRWEB) , ... August 16, 2017 , ... Summer ... Long Island’s original family-owned supermarket, has put together suggestions for enjoying the season of ... recipe or activity, everyone in the family can join in on the fun. ...
(Date:8/16/2017)... , ... August 16, 2017 , ... Ten outstanding teachers ... Stars in the Classroom and will win a visit by a Houston Texans player, ... who are at least five years old can visit texanschecking.com/stars to nominate their favorite ...
(Date:8/16/2017)... York, New York (PRWEB) , ... August 16, 2017 , ... ... they could minimize its appearance with diet and exercise. In fact, cellulite can't always ... is a safer and more effective treatment available to select physicians nationwide. Dr. Kenneth ...
(Date:8/16/2017)... ... August 16, 2017 , ... Paul Vitenas, MD, ... Connolly 2017 Top Doctor. The annual list identifies the nation’s top physicians, in a ... has made it to the top of Castle Connolly’s coveted ranking. , Castle Connolly ...
(Date:8/16/2017)... (PRWEB) , ... August 16, 2017 , ... Melbourne’s reign ... by the prestigious Economist Intelligence Unit’s (EIU) annual Liveability Index. , The Index surveys ... Since the index began in 2006, Melbourne has consistently come in the top three ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... Zimmer Biomet Holdings, Inc. (NYSE and SIX: ZBH), a global ... Directors has approved the payment of a quarterly cash dividend ... The cash dividend of $0.24 per ... to stockholders of record as of the close of business ... to approval of the Board of Directors and may be ...
(Date:8/7/2017)... 2017  Diplomat Pharmacy, Inc. (NYSE: DPLO), the nation,s largest ... June 30, 2017.  All comparisons, unless otherwise noted, are to ... Second Quarter 2017 Highlights include: ... an increase of 3.5% Total prescriptions dispensed ... of 7.5% versus 7.6% Gross profit ...
(Date:8/4/2017)... The search for test results that can ... has long been the goal of healthcare providers and ... the largest meeting of lab professionals and IVD firms ... firm Kalorama Information.  The firm said scores of companies ... supplies and software were at the American Association for ...
Breaking Medicine Technology: