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:10/13/2017)... ... October 13, 2017 , ... As health professionals work to improve ... engagement.” The patient is doing more than filling out a survey; in many cases ... an increasing emphasis in health care and research on the importance of active engagement ...
(Date:10/13/2017)... , ... October 13, 2017 , ... PurhealthRX , ... Oil utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize ... providing a CBD form that can be easily incorporated into liquid products, while reducing ...
(Date:10/13/2017)... ... 13, 2017 , ... Many families have long-term insurance that covers care for ... a waiver for care if the client has a cognitive impairment diagnosis. , ... care, is often waived, so the benefits from their insurance start immediately,” said Mechell ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer ... one of the most popular and least understood books in the Holy Scriptures, Revelation. ... descriptions that have baffled scholars for centuries. Many have tossed it off as mere ...
(Date:10/13/2017)... ... ... “America On The Brink”: the Christian history of the United States and the loss ... author, William Nowers. Captain Nowers and his wife, Millie, have six children, ten ... the Navy. Following his career as a naval aviator and carrier pilot, he ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... 2017  NDS received FDA 510(k) clearance in May 2017 for ... stand specifically designed for endoscopy environments. An innovative secondary monitor solution, ... solution to support the improvement of patient outcomes, procedural efficiency, and ... ... ...
(Date:10/7/2017)... , Oct. 6, 2017   Provista, a ... than $100 billion in purchasing power, today announced a ... information. The Newsroom is the online home ... trends, infographics, expert bios, news releases, slideshows and events. ... to a wealth of resources at their fingertips, viewers ...
(Date:10/4/2017)... , Oct. 4, 2017  South Korean-based healthcare product ... training aide "cprCUBE" on Kickstarter. The device will educate ... cardiac arrests with better efficiency compared to the dated ... real-time feedback on efficacy of the compression for a ... has a goal to raise $5,000. ...
Breaking Medicine Technology: