Navigation Links
Uncommon BRAF mutation in melanoma sensitive to MEK inhibitor drug therapy
Date:7/16/2012

An uncommon mutation of the BRAF gene in melanoma patients has been found to respond to MEK inhibitor drugs, providing a rationale for routine screening and therapy in melanoma patients who harbor the BRAF L597 mutation.

The new study by co-first-authors Kimberly Brown Dahlman, Ph.D., Junfeng Xia, Ph.D., and Katherine Hutchinson, B.S., Vanderbilt-Ingram Cancer Center (VICC), Nashville, Tenn., was published online July 14 in Cancer Discovery. The research was led by co-senior authors William Pao, M.D., Ph.D., Jeffrey Sosman, M.D., and Zhongming Zhao, Ph.D., VICC, and Antoni Ribas, M.D., Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, Calif.

Mutations in BRAF V600E or KIT are common in about 40 percent to 50 percent of melanomas, and drugs that block or inhibit BRAF V600E were recently approved for treatment of melanoma patients with these mutations. However, there has been no effective treatment for patients with wildtype (WT) melanoma that is negative for these driver mutations.

To uncover other potentially targetable mutations, the investigators studied the tumor from a 75-year-old patient with an aggressive form of melanoma which was negative for the BRAF V600E mutation. They performed whole genome sequencing on the tumor, along with DNA from matched blood, and confirmed a mutation at BRAF L597.

To determine how many similar mutations might be overlooked by assessing only the BRAF V600 position, they analyzed the mutational status of 49 additional tumor samples negative for V600, as well as recurrent mutations in NRAS and KIT. Two of the tumors (4 percent) were found to have BRAF L597 mutations and a third tumor harbored a BRAF K601E mutation.

BRAF L597 and K601 are adjacent to V600. Since V600 mutants are sensitive to both BRAF and MEK inhibitor drugs, the investigators tested whether the BRAF inhibitor drug vemurafenib and a MEK inhibitor drug could inhibit cell proliferation signals induced by these mutants in cell lines. The MEK inhibitor led to a dramatic shut down of signaling, suggesting that tumors harboring BRAF L597 and K601 mutations might benefit from treatment with MEK inhibitors.

Confirming this hypothesis, a 69-year-old patient with metastatic melanoma harboring a BRAF L597S mutation experienced significant disease shrinkage after two cycles on therapy with a MEK inhibitor drug called TAK-733, currently in Phase I clinical trials. The patient was disease progression-free after more than 24 weeks.

The authors believe these data demonstrate that BRAF L597 mutations have clinical significance in melanoma. Further study is needed to confirm these findings.


'/>"/>

Contact: Dagny Stuart
dagny.stuart@vanderbilt.edu
615-936-7245
Vanderbilt University Medical Center
Source:Eurekalert

Related medicine news :

1. KRAS gene mutation and amplification status affects sensitivity to antifolate therapy
2. Researchers Find Gene Mutations That May Be a Key to Autism
3. Mayo Clinic breast cancer study finds new type of mutation
4. Scientists make breakthrough in bile duct cancer with discovery of new gene mutations
5. Cancer may require simpler genetic mutations than previously thought
6. Mutations impair childhood growth and development by disrupting organization of chromosome pairs
7. Study sheds new light on role of genetic mutations in colon cancer development
8. Mutations in JAK3 gene identified in subtype of lymphoma provide potential drug target
9. Study finds new gene mutations that lead to enlarged brain size, cancer, autism, epilepsy
10. Gene Mutation Linked to Facial, Skull Abnormalities
11. Mutation in gene IDH a possible target for AML treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/21/2017)... ... ... Seamild, the largest manufacturer of oats in China, is now aiming at global ... is recognized globally as one of the healthiest cereals, XieQingkui, the founder of Seamild, ... move to sow the seed of good karma. Buddhism spirit featuring benevolence and sacrifice ...
(Date:1/21/2017)... Pekin, IL (PRWEB) , ... January 21, 2017 , ... ... disorders. Even when individuals experience the freedom of recovery, they often feel shame for ... abuse and post-traumatic stress disorder (PTSD). In the workshop, “Rising Strong in Life After ...
(Date:1/20/2017)... ... January 20, 2017 , ... Source Vitál Apothecary, a skin and ... essential oils, announced the company had a successful visit to the 2017 ECRM Diet, ... gives companies that work in the nutritional, sports and health industries a chance to ...
(Date:1/20/2017)... ... January 20, 2017 , ... International Protein, a company based out ... announced it attended the January ECRM trade show in Hilton Head, SC. , ... was determined to create a line of products that would elevate her fitness regime. ...
(Date:1/20/2017)... ... ... “The Angel”: a heartwarming and earnest tale of faith and believing in the ... is the creation of published author, Marjorie Lund-Fontaine, a former professional violinist, alumnus of ... asked of her new book, Marjorie says, “‘The Angel’ was written as a fairytale, ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... , Jan. 19, 2017 Conference Call and Webcast to ... ) today announced it will release results for the fourth quarter ... ... host a conference call at 4:30 PM ET on Wednesday, February ... full year 2016 financial results and other corporate activities. To participate ...
(Date:1/19/2017)... , Jan. 19, 2017 This report ... current and future scenario of the global market. Large ... opioid consumption. Severe chronic constipation is a major side ... traditional laxatives. Hence, novel targeted therapy has been prescribed ... sufferers, launch of targeted medicines, and growing awareness about ...
(Date:1/19/2017)...  Stealth BioTherapeutics Inc. ( Stealth ), a clinical-stage ... announced new additions to its senior leadership team: ... and Daniel Geffken as interim Chief Financial ... , Pharm.D. has been promoted to Chief Clinical Development ... Doug and Daniel to our management team, as both ...
Breaking Medicine Technology: