Featured Research

from universities, journals, and other organizations

Genes that may help predict response to BRAF inhibitors for advanced melanoma identified

Date:
June 1, 2011
Source:
University of Pennsylvania School of Medicine
Summary:
Genetic analysis of the tumors from patients with advanced melanoma can clue researchers in to how well patients will respond to therapies targeting the growth-promoting protein called BRAF, researchers report. Looking outside of the BRAF gene, the researchers found loss of the tumor suppressor gene PTEN also appears to be associated with patient response to GSK436.

Genetic analysis of the tumors from patients with advanced melanoma can clue researchers in to how well patients will respond to a therapy that targets the growth-promoting protein called BRAF, a researcher from the Perelman School of Medicine at the University of Pennsylvania will report on June 6 at the annual meeting of the American Society of Clinical Oncology. Looking outside of the BRAF gene, the researchers found loss of the tumor suppressor gene PTEN also appears to be associated with patient response to GSK436, which could help guide researchers to even more personalized approaches to melanoma therapy.

The phase I clinical trial data highlight the role that genetic changes other than that in BRAF may play in a patient's resistance to BRAF inhibitors, a targeted therapy that has shown unprecedented efficacy among patients with metastatic disease.

"These findings are important because they suggest that performing genetic characterization of melanomas for genetic changes outside of BRAF could help predict the patients that may have worse responses to BRAF inhibitors," says Katherine Nathanson, MD, an associate professor of Medical Genetics in Penn's Abramson Cancer Center, who led the study. Armed with such information, a physician could prescribe a different drug or combination of drugs to target these advanced cancers. Guiding such decisions early can save time in the race to control metastatic melanomas, which commonly kill patients within a year after they're identified.

An estimated 40 to 60 percent of all melanomas carry a mutated BRAF gene. Although patients with advanced melanoma are often resistant to chemotherapy, drugs that go after the overactive BRAF protein -- which acts as a foot on a gas pedal promoting tumor growth -- have demonstrated promising results in Phase I and II trials. Research shows that as many as 80 percent of patients who take these drugs experience a clinical benefit. However, despite signs of initial success, months into receiving the therapy, the tumors of many patients receiving the BRAF inhibitor return and begin growing again.

"There has been a lot of focus on what happens with tumors as they develop resistance to BRAF inhibitors," Nathanson says. "We asked a different question: Are there mutations that help predict response to inhibitors before the patients begin drug treatment?"

Through a collaboration with GlaxoSmithKline, Nathanson's group obtained tumors from patients enrolled in a phase I trial of BRAF inhibitor GSK436. To date, the researchers have performed genomic profiling on the melanomas of 32 patients prior to beginning treatment with GSK436. "This unique sample set allowed us to systematically look at additional predictors for response to BRAF inhibitors," Nathanson says.

Her team found that patients with clear loss of PTEN genetically have a shorter period of progression free survival (4.2 months) on GSK436, as compared to those with normal PTEN (7.4 months). However, the numbers of patients are small and larger cohorts will be needed to confirm this preliminary finding. Mutations in several other genes believed to play a role in cancer, including MEK2 and CDK4, were also identified in two patients; however additional data are needed to clarify the predictive value of such mutations to BRAF inhibitors. Exploratory analysis also was done looking at the copy number of genes known to be important in melanoma. The presence of additional copies of CDKN2A, which is associated with tumor suppression, was significantly associated with an improvement in outcome.

"Because BRAF inhibitors will likely receive FDA approval soon, it's important to understand what additional factors will predict the patients who will be most helped by the drugs," Nathanson says. "Understanding what additional genetic changes are present in melanomas taken directly from patients paves the way for the development of combination therapies."


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of Pennsylvania School of Medicine. "Genes that may help predict response to BRAF inhibitors for advanced melanoma identified." ScienceDaily. ScienceDaily, 1 June 2011. <www.sciencedaily.com/releases/2011/06/110601152055.htm>.
University of Pennsylvania School of Medicine. (2011, June 1). Genes that may help predict response to BRAF inhibitors for advanced melanoma identified. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2011/06/110601152055.htm
University of Pennsylvania School of Medicine. "Genes that may help predict response to BRAF inhibitors for advanced melanoma identified." ScienceDaily. www.sciencedaily.com/releases/2011/06/110601152055.htm (accessed April 17, 2014).

Share This



More Health & Medicine News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins