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:6/23/2017)... ... , ... Goodcents Deli Fresh Subs today announced the opening of a new ... St. Topeka, Kan. 66604 (near 21st and Gage). It is owned and operated by ... locations in the Topeka and Bonner Springs, Kan. area. , “Goodcents has such ...
(Date:6/23/2017)... ... June 23, 2017 , ... Ensuring meat products have reached ... the importance of correctly using a meat thermometer. The videos feature University of ... on consumer food safety habits. Dr. Bruhn explains the variety of meat thermometers ...
(Date:6/23/2017)... , ... June 23, 2017 , ... 21 Middle East ... (EF) has selected 21 leaders from government, business and civil society in 11 countries ... the U.S. this fall, engaging in a transformative exchange of knowledge and ideas with ...
(Date:6/23/2017)... ... June 23, 2017 , ... PureLife Dental is pleased to announce that California ... members. As part of the amalgam separator endorsement, all CDA members may purchase an ... off the retail value. This partnership between PureLife and CDA is especially timely as ...
(Date:6/23/2017)... ... June 23, 2017 , ... American Farmer, will feature ... which is slated to air fourth quarter 2017. American Farmer airs Tuesdays at 8:30aET ... a Danish pharmacist, founded Chr. Hansen in Denmark in 1874 after a groundbreaking discovery ...
Breaking Medicine News(10 mins):
(Date:6/9/2017)... AirXpanders, Inc. (ASX: AXP) (AirXpanders or Company), ... sale and distribution of the AeroForm® Tissue Expander System, ... commercial roll-out in the United States ... hundred (100) medical institutions and health systems, located throughout ... alternative for women who choose reconstructive surgery following a ...
(Date:6/8/2017)... June 8, 2017   Responding to Heath Ledger,s ... the death of singer Chris Cornell in May, ... International offers a free online psychiatric drug ... and families about psychotropic drug risks. The ... died from an accidental overdose, has called for tighter rules ...
(Date:6/7/2017)... , June 7, 2017  Novavax, Inc., (Nasdaq: ... two Phase 2 trials of its RSV F protein recombinant ... bearing age have been published in the journal ... been shared in prior scientific conferences). The Company previously announced ... 2014. Novavax is developing the RSV F Vaccine with the ...
Breaking Medicine Technology: