Featured Research

from universities, journals, and other organizations

Drug shown to reverse radioiodine resistance in some advanced thyroid cancers

Date:
February 13, 2013
Source:
Memorial Sloan-Kettering Cancer Center
Summary:
Researchers have found that the investigational drug selumetinib shuts down the signaling of genetic mutations that prevent some patients' thyroid cancer tumors from absorbing radioiodine, the most effective treatment for the disease.

The experimental drug selumetinib may allow some patients with advanced thyroid cancer to overcome resistance to radioiodine (RAI), the most effective therapy for the disease, according to new research from Memorial Sloan-Kettering Cancer Center.

Published in the Feb. 14 issue of the New England Journal of Medicine, the study offers new hope for patients with a disease that can have a poor prognosis. An estimated 56,000 new cases of thyroid cancer are diagnosed each year in the United States, and that number is on the rise, according to the National Cancer Institute. About 5 percent of these patients will eventually develop distant metastatic disease, and the ten-year survival rate for patients with metastatic tumors that fail to respond to RAI is approximately 10 percent.

According to James A. Fagin, MD, Memorial Sloan-Kettering's Endocrinology Service Chief and senior author on the study, many trials have tested strategies for overcoming RAI resistance in metastatic thyroid cancers, but none have been successful. Previous studies have shown that a cell's ability to absorb RAI is controlled by the MAPK pathway, so Dr. Fagin and his colleagues examined whether selumetinib, an MAPK inhibitor, could reverse RAI resistance by inhibiting the signaling of genetic mutations in this pathway. The approach proved effective, especially in patients with thyroid cancers that contain a mutation in the RAS gene -- a component of the MAPK pathway.

"Blocking this key pathway increased the uptake of iodine, making radioiodine treatment potentially effective once again," said Fagin, who led this research in cells and in mice.

Following a five-day low-iodine diet, researchers administered selumetinib to 20 patients with tumors resistant to radioiodine. After four weeks, patients underwent a diagnostic scan that measured how much RAI their tumors would absorb. In eight patients, including all five with an NRAS gene mutation, selumetinib increased iodine uptake enough to allow patients to undergo RAI therapy.

Following RAI, five patients had confirmed partial responses and three had stable disease. In seven of the eight patients, outcomes remained unchanged during six months of follow-up. All eight patients had a decreased level of serum thyroglobulin -- a protein in the blood used to screen for advanced thyroid cancer -- and none experienced serious side effects from selumetinib.

"An advantage of this therapeutic strategy is that only a short course of drug therapy is required to elicit a significant clinical effect," Fagin said, adding that "the initial results show promise for RAS-mutant disease, but the hope is that a larger trial will shed light on whether selumetinib can be effective for a broader range of advanced thyroid cancer subtypes."

Memorial Sloan-Kettering will lead the international, multicenter phase III clinical trial of selumetinib later this year. The trial, which will be sponsored by AstraZeneca, will enroll patients who have recently had their thyroid gland removed -- a procedure known as total thyroidectomy -- due to thyroid cancer that has spread to nearby tissue or lymph nodes.


Story Source:

The above story is based on materials provided by Memorial Sloan-Kettering Cancer Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Alan L. Ho, Ravinder K. Grewal, Rebecca Leboeuf, Eric J. Sherman, David G. Pfister, Desiree Deandreis, Keith S. Pentlow, Pat B. Zanzonico, Sofia Haque, Somali Gavane, Ronald A. Ghossein, Julio C. Ricarte-Filho, José M. Domínguez, Ronglai Shen, R. Michael Tuttle, Steve M. Larson, James A. Fagin. Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer. New England Journal of Medicine, 2013; 368 (7): 623 DOI: 10.1056/NEJMoa1209288

Cite This Page:

Memorial Sloan-Kettering Cancer Center. "Drug shown to reverse radioiodine resistance in some advanced thyroid cancers." ScienceDaily. ScienceDaily, 13 February 2013. <www.sciencedaily.com/releases/2013/02/130213173141.htm>.
Memorial Sloan-Kettering Cancer Center. (2013, February 13). Drug shown to reverse radioiodine resistance in some advanced thyroid cancers. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2013/02/130213173141.htm
Memorial Sloan-Kettering Cancer Center. "Drug shown to reverse radioiodine resistance in some advanced thyroid cancers." ScienceDaily. www.sciencedaily.com/releases/2013/02/130213173141.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) — Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) — In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) — A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) — The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. 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