Navigation Links
Moffitt Cancer Center researchers working at frontiers of melanoma research

At Moffitt Cancer Center, patients with stage III and IV unresectable melanoma are now routinely genetically profiled for several gene mutations, including the BRAF gene, a known driver oncogene for melanoma. Research has shown that mutations in the BRAF gene determine sensitivity or resistance to a class of drugs that are BRAF inhibitors.

"We have found that a large number of patients with melanoma who have the BRAF gene mutation quickly develop resistance to drugs that are BRAF inhibitors," said Jeffrey S. Weber, M.D., Ph.D., director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt. "A recent approach in the melanoma research community is to find ways to overcome resistance to drugs we targeted to mutated BRAF."

At Moffitt, researchers have access to a large database of patient-donated tissues through Moffitt's Total Cancer Care program, a far-reaching design for care that includes building a biorepository of tumor samples for study and patient selection for clinical trials participation. By looking for patient genetic profiles for BRAF, Moffitt researchers are working at the frontiers of personalized medicine, which is the effort to match the right patient to the right drug.

According to Weber, although 50 percent of melanoma patients might have the BRAF mutation, the lack of other valid molecular targets for melanoma has "hampered efforts to individualize therapy."

That may have changed now that the U.S. Food and Drug Administration approved the drug Vemurafenib for melanoma patients who test positive for the BRAF mutation.

An international team of researchers, including those at Moffitt led by Weber, found that when tested in a phase II clinical trial, Vemurafenib was highly effective for patients with previously treated metastatic melanoma that had the BRAF mutation.

The study was published in a recent issue of The New England Journal of Medicine (366;8).

However, Moffitt researchers know that patients can develop resistance to Vemurafenib and, consequently tested six different models of Vemurafenib resistance against an "inhibitor" called XL888. Their findings appeared in a recent issue of Clinical Cancer Research, a publication of the American Association for Cancer Research.

"We found that the inhibitor XL888 overcomes Vemurafenib resistance through a number of mechanisms," said Keiran S. Smalley, Ph.D., of Moffitt' s Departments of Molecular Oncology and Cutaneous Oncology and who is a colleague of Weber and the senior author on the study.

According to Smalley, there was already evidence that one of a family of inhibitors called HSP90 could overcome multiple drug chemotherapy resistance mechanisms in a number of cancers, including non-small cell lung cancer and breast cancer. They hoped it would help arrest the cancer cell cycle in melanoma cell lines resistant to the BRAF inhibitors.

"Responses to XL888 were highly durable, with no resistant colonies emerging after four weeks of treatment," Smalley said. "In control studies not using XL888, resistant colonies emerged in every case."

For Weber, the success of Vemurafenib represents "the single most dramatic improvement in the treatment of melanoma in 20 years."

"The 53 percent response rate on the Vemurafenib study for previously treated melanoma patients with the BRAF mutation was significantly better than response rates seen in studies of other therapies for melanoma," Weber said. "To be able to find a mutation through gene profiling and develop a test to match a patient to the best treatment for them is the kind of personalized medicine we want to be known for at Moffitt."


Contact: Patty Kim
H. Lee Moffitt Cancer Center & Research Institute

Related medicine news :

1. Moffitt Cancer Center and GLG Pharma, LLC sign licensing agreement to develop the next generation of targeted anti-cancer therapeutics
2. Moffitt Cancer Center and GLG Pharma LLC sign licensing agreement to develop the next generation of targeted anti-cancer therapeutics
3. Moffitt Cancer Center researchers use new tool to counter multiple myeloma drug resistance
4. Moffitt researchers find possible key to preventing chemotherapy resistance in ovarian cancer
5. Moffitt Cancer Center researchers find more clues to causes of breast cancer
6. Moffitt Cancer Center researchers find regulatory T-cell clue to help prevent GVHD
7. Moffitt Cancer Center researchers unravel biochemical factor important in tumor metastasis
8. Moffitt Cancer Center researchers find men less willing to be screened for cancer
9. Moffitt Cancer Center researchers find MK1775 active against sarcomas
10. Moffitt researchers will be strong participants in American Society of Hematology meeting
11. Moffitt Cancer Center researchers find potential target for treating metastatic cancer
Post Your Comments:
(Date:12/1/2015)... , ... December 01, 2015 , ... According to an ... groups has filed a discrimination claim against the U.S. Department of Health and Human ... Affordable Care Act (ACA) plans are breaking the clause in the law prohibiting the ...
(Date:12/1/2015)... ... December 01, 2015 , ... Califia Farms , one ... its iconic bottle has won top honors in Beverage World Magazine’s Global Packaging Design ... announced that it has been selected as a 2015 U.S.A. Taste Champion in the ...
(Date:12/1/2015)... ... , ... Growth in medical payments per workers’ compensation claim in Louisiana slowed ... nonhospital care, according to a recent study by the Workers Compensation Research Institute (WCRI). ... medical payments per claim with more than seven days of lost time continued to ...
(Date:12/1/2015)... ... December 01, 2015 , ... CloudLIMS today announced ... Bridge Business Awards under the New Products and Services category for its innovative ... sample management software that helps labs organize data and track samples with ...
(Date:12/1/2015)... ... December 01, 2015 , ... Diabetic foot wounds ... Podiatrists are well aware that psychology-based patient non-compliance (disobedience of a health care ... to diseases of the diabetic foot. The American Board of Multiple Specialties ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... 1, 2015 --> ... report "Nucleic Acid Labeling Market by Product (Reagents & ... Primer, In Vitro Transcription, Reverse Transcription, End Labeling), by ... The global market is expected to reach USD 1,925.7 ... growing at a CAGR of 8.65%. Browse ...
(Date:12/1/2015)... Russia has always been a country of choice for ... Europe in 2015 were tested in phase II-III ... has always been a country of choice for global multi-center phase ... in 2015 were tested in phase II-III clinical trials ... always been a country of choice for global multi-center phase III clinical ...
(Date:12/1/2015)... Dec. 1, 2015 Relmada Therapeutics, Inc. (OTCQB: RLMD), ... chronic pain, announced today that the company will present at ... December 1-3 at the Luxe Sunset Boulevard Hotel in ... CEO of Relmada Therapeutics, will present on Thursday, December 3, ... . Please register at least 10 minutes prior ...
Breaking Medicine Technology: