(Press-News.org) 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.
INFORMATION:
Other researchers who participated in the study include: Mohammad Atefi, Ph.D., Suzanne Branch, CCRC and John Glaspy, M.D., MPH, UCLA; Neal Rosen, M.D., Ph.D., and David Solit, M.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y.; Donald Hucks, M.S., Peilin Jia, Ph.D., Zengliu Su, M.D., Ph.D., Pamela Lyle, M.D., Donna Hicks, B.S., James Netterville, M.D., and Cindy Vnencak-Jones, Ph.D., Vanderbilt; and Viviana Bozon, M.D., Millennium Pharmaceuticals, Cambridge, Mass.
Funding was provided by the National Cancer Institute (NCI), a division of the National Institutes of Health (NIH) - VICC Cancer Center Core Grant (CA68485), 5K24 CA97588‐06 (JS) and P01CA129243, the T.J. Martell Foundation, the Kleberg Foundation, the Seaver Institute, the Wesley Coyle memorial fund, the Garcia‐Corsini family fund, Harry J. Lloyd Charitable Trust (PIP), the American Cancer Society (Mary Hendrickson‐Johnson Melanoma Professorship to JS), Stand Up to Cancer SU2C-AACR-IRG0109 (WP), The James C. Bradford Family Foundation, and an anonymous donor. Treatment with TAK‐733 was supported through a clinical trial from Millennium Pharmaceuticals.
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SAN ANTONIO (July 16, 2012) — A novel technique for measuring tiny, rapid-fire secretions in the brains and mouthparts of fruit flies (drosophila) is providing insights into the beneficial effects of eating less — information that ultimately could help people suffering from neuromuscular disorders.
Using the method, researchers uncovered never-before-seen brain chemistry that helps explain why fruit flies genetically manipulated to mimic conditions such as Parkinson's disease and myasthenia gravis are more vigorous and live longer when fed a restricted diet.
Published ...
COLUMBIA, Mo. — A team of University of Missouri researchers has found that introducing a missing gene into the central nervous system could help extend the lives of patients with Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile death in the world.
SMA is a rare genetic disease that is inherited by one in 6,000 children who often die young because there is no cure. Children who inherit SMA are missing a gene that produces a protein which directs nerves in the spine to give commands to muscles.
The MU team, led by Christian Lorson, professor in ...
U of S researchers have discovered the chemical pathway that Cannabis sativa uses to create bioactive compounds called cannabinoids, paving the way for the development of marijuana varieties to produce pharmaceuticals or cannabinoid-free industrial hemp. The research appears online in the July 16 early edition of the Proceedings of the National Academy of Sciences (PNAS).
U of S adjunct professor of biology Jon Page explains that the pathway is an unusual one, involving a specialized version of one enzyme, called hexanoyl-CoA synthetase, and another enzyme, called olivetolic ...
When Olympic athletes throw up their arms, clench their fists and grimace after a win, they are displaying triumph through a gesture that is the same across cultures, a new study suggests. New findings due to be published in the journal Evolution and Human Behavior suggest this victory pose signals feelings of triumph, challenging previous research that labeled the expression pride.
"We found that displays of triumph include different behaviors to those of pride and occur more immediately after a victory or win," said David Matsumoto, professor of psychology at San Francisco ...
Montreal, July 16, 2012 – Statistics show that today, almost one in four Canadians is obese. A deadly trend that has been on the rise for the last thirty years, obesity is associated with diabetes, heart disease and cancer. But is the obesity epidemic putting more pressure on an already strained Canadian health care system?
James McIntosh, a professor in the Department of Economics at Concordia University, is the first to look at the impact of obesity on the number of doctor visits nation-wide.
According to his research, obese individuals visit the doctor more frequently ...
LA JOLLA, CA----For more than 20 years, doctors have been using cells from blood that remains in the placenta and umbilical cord after childbirth to treat a variety of illnesses, from cancer and immune disorders to blood and metabolic diseases.
Now, scientists at the Salk Institute for Biological Studies have found a new way-using a single protein, known as a transcription factor-to convert cord blood (CB) cells into neuron-like cells that may prove valuable for the treatment of a wide range of neurological conditions, including stroke, traumatic brain injury and spinal ...
The following highlights summarize research papers that have been recently
published in Journal of Geophysical Research-Biogeosciences (JGR-G), Journal
of Geophysical Research-Atmospheres (JGR-D), Journal of Geophysical
Research-Planets (JGR-E), Geochemistry, Geophysics, Geosystems (G3), and
Geophysical Research Letters (GRL).
1. Droughts threaten Bornean rainforests
At 130 million years old, the rainforests of Southeast Asia are the oldest in the world
and home to thousands of plant and animal species, some endemic to these forests.
The rainforests ...
The American Association for the Advancement of Science (AAAS) has joined more than 3000 national, state, and local organizations in warning the U.S. Congress and President Barack Obama that automatic budget cuts set for January could have "devastating" effects on research, education, social services, security, and international relations.
The planned cuts threaten federal programs that "support economic growth and strengthen the safety and security of every American in every state and community across the nation," the groups wrote in a 12 July letter to Congress. "We ...
HOUSTON – (July 16, 2012) – Researchers at Rice University and Lockheed Martin reported this month that they've found a way to make multiple high-performance anodes from a single silicon wafer. The process uses simple silicon to replace graphite as an element in rechargeable lithium-ion batteries, laying the groundwork for longer-lasting, more powerful batteries for such applications as commercial electronics and electric vehicles.
The work led by Sibani Lisa Biswal, an assistant professor of chemical and biomolecular engineering at Rice, and lead author Madhuri Thakur, ...
Poor people hold more traditional values toward marriage and divorce than people with moderate and higher incomes, UCLA psychologists report in the current issue of the Journal of Marriage and Family.
The findings are based on a large survey about marriage, relationships and values, analyzed across income groups. They raise questions about how effectively some $1billion in government spending to promote the value of marriage among the poor is being spent.
"A lot of government policy is based on the assumption that low-income people hold less traditional views about ...
