Navigation Links
KRAS gene mutation and amplification status affects sensitivity to antifolate therapy
Date:4/4/2012

CHICAGO Testing patients with non-small cell lung cancer for both mutations and amplifications of the KRAS gene prior to therapy may help to predict response to treatment with antifolates, according to the updated results of a preclinical study presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

Patients, especially those with lung cancer, who have KRAS gene mutations have a worse prognosis and do not respond well to targeted therapies, according to Sarah Bacus, Ph.D., Quintiles senior vice president and chief scientific officer of translational research and development, oncology. The results suggest that although these mutations are linked to a poor response to targeted therapies, they may predict response to treatment with antifolates, as long as the number of mutant genes is not amplified.

She and her colleagues assessed the relationship between antifolate medications and KRAS mutations and amplification, where the gene has an excess number of copies.

The preliminary results of the study were presented in November at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics. Researchers treated human non-small cell lung cancer cell lines (KRAS wild type, KRAS-mutant nonamplified and KRAS-mutant amplified) with the antifolates methotrexate or pemetrexed.

In lung cancer, the KRAS-mutant tumors need the folate pathway, which is associated with the growth of cancer. Treatment with the antifolate pemetrexed led to dramatic responses in patients with KRAS-mutant lung cancer. Patients with KRAS-wild type were less responsive. The researchers found a similar trend in KRAS-mutant lung cancer cell lines. When cell lines with KRAS mutations were deprived of access to this pathway, they failed to grow. However, this response was not seen if the number of copies of the KRAS-mutant gene was amplified or if the KRAS was wild type.

"KRAS mutations are most frequently observed in pancreatic, colorectal, lung, endometrial and biliary tract cancers, and as such, antifolates may have utility in the treatment of these cancers alone or in combination with other chemotherapies such as DNA-damaging agents," Bacus said.

She recommended that before prescribing an antifolate, whether in lung cancer or other cancers where KRAS mutations are prevalent, physicians should test for KRAS mutation and amplification, because the study results suggest that patients are likely to respond well only if the KRAS gene is mutated and not amplified.


'/>"/>
Contact: Jeremy Moore
Jeremy.Moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Stealth properties of cancer-causing genetic mutations identified
2. Gene mutation discovery sparks hope for effective endometriosis screening
3. Cancer sequencing initiative discovers mutations tied to aggressive childhood brain tumors
4. Mutations in 2 Genes Linked to Rare Autism-Related Disorder
5. Gene Mutations May Boost Ovarian Cancer Survival: Study
6. Women with certain type of ovarian cancer and BRCA gene mutation have improved survival at 5 years
7. UNC scientists collaborate to find first major genetic mutation associated with hereditary prostate cancer risk
8. Gene Mutation Linked to Chemo-Resistant Colon Cancer
9. Gene Mutations Linked to Thyroid Cancer Risk: Study
10. Gene Mutation May Be Key to Familial Pancreatic Cancer
11. Research Sheds Light on Gene Mutations Role in Rare Tumors
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... , ... Mediaplanet is proud to announce the launch of ... treatments, therapeutic technologies, and revolutionized nutrition that are helping patients and physicians manage ... in the last 3 decades,” says Dr. Valentine Fuster, a world-renowned cardiologist. “This ...
(Date:12/2/2016)... ... , ... Rijuven Corp launches rejiva ( http://www.rejiva.com ), a unique wearable technology ... health technology on the market can deliver all that rejiva can. , “Rejiva promotes ... their health than the usual heart rate and steps taken”, adds Evens Augustin, CEO ...
(Date:12/2/2016)... ... December 02, 2016 , ... Today ... intelligent, connected applications, was named the best Sales Team of 2016 as part ... was made today by the Software & Information Industry Association (SIIA), the principal ...
(Date:11/30/2016)... ... , ... "I hate when the mixture of saliva and toothpaste runs down ... from Bridgewater, N.J. "I thought that there had to be a way to prevent ... patent-pending DEFLECTOR to prevent saliva and toothpaste from running down the brush handle onto ...
(Date:11/30/2016)... U.K. (PRWEB) , ... November 30, 2016 , ... ... address the tech functions and stylish design wanted by today’s consumers at an ... Cronovo Co-Founder Darin Philip says the new watch is “a game changer” when ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... WOONSOCKET, R.I. , Dec. 2, 2016 ... hold its annual Analyst Day in New York City on Thursday, December ... the CVS Health leadership team will provide an in-depth ... and enhance shareholder value. The company will also discuss ... audio and video webcast of the event will be ...
(Date:12/2/2016)... 2, 2016 Orthopedic Implants (Including Spinal ... Expected to Gain a Significant Market Share Owing to a ... ... According to a new report by ... Sterile Packaging: Clamshell Product Type Segment Projected to Witness a ...
(Date:12/2/2016)... N.J. , Dec. 2, 2016   CytoSorbents ... immunotherapy leader commercializing its European Union approved CytoSorb ... and cardiac surgery patients worldwide, announced that Dr. ... the 9th Annual LD Micro Main Event ... , 2016 at the Luxe Sunset Boulevard Hotel in ...
Breaking Medicine Technology: