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Archive - Sep 29, 2012

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Combination of Targeted Treatment Drugs Delays Resistance in Melanoma Patients

Combined treatment with two drugs targeting different points in the same growth-factor pathway delayed the development of treatment resistance in patients with BRAF-positive metastatic malignant melanoma. The results of a phase I/II study of treatment with the kinase inhibitors dabrafenib and trametinib were published online on September 29, 2012 in the New England Journal of Medicine (NEJM) and are being released online to coincide with a presentation at the European Society for Medical Oncology meeting in Vienna. "We investigated this combination because of research we and others have conducted into the molecular underpinnings of resistance to BRAF inhibitor therapy," says Keith Flaherty, M.D., of the Massachustts General Hospital (MGH) Cancer Center, lead author of the NEJM report and principal investigator of the study. "We found that adding the MEK inhibitor trametinib to BRAF inhibitor dabrafenib clearly delays the emergence of resistance. In fact, the combination was at least twice as effective as BRAF inhibition alone." In approximately half of patients with metastatic melanoma, tumor growth is driven by mutations that keep the BRAF protein – part of the MAPK cell growth pathway – constantly activated. In recent years, drugs that inhibit BRAF activity have rapidly halted and reversed tumor growth in about 90 percent of treated patients, but most patients' response is temporary, with tumor growth resuming in six or seven months. Investigations into how this resistance emerges have suggested that the MAPK pathway gets turned back on through activation of MEK, another protein further down the pathway. Based on promising results of animal studies, the current investigation was designed to test whether inhibiting both the BRAF and MEK proteins could delay treatment resistance.

New, Rabies-Related Virus Caused Death in the Congo

An isolated outbreak of a deadly disease known as acute hemorrhagic fever, which killed two people and left one gravely ill in the Democratic Republic of Congo in the summer of 2009, was probably caused by a novel virus scientists have never seen before. Described online on September 27, 2012 in the open-access journal PLoS Pathogens, the new microbe has been named Bas-Congo virus (BASV) after the province in the southwest corner of the Congo where the three people lived. It was discovered by an international research consortium that included scientists from the University of California, San Francisco (UCSF) and the University of California, Davis, Global Viral, the Centre International de Recherches Médicales de Franceville in Gabon, the Institut National de Recherche Biomédicale, Kinshasa in the Democratic Republic of the Congo, Metabiota, and others. “Known viruses, such as Ebola, HIV, and influenza, represent just the tip of the microbial iceberg,” said Joseph Fair, Ph.D., a co-author and vice president of Metabiota. “Identifying deadly unknown viruses, such as Bas-Congo virus, gives us a leg up in controlling future outbreaks.” “These are the only three cases known to have occurred, although there could be additional outbreaks from this virus in the future,” said Charles Chiu, M.D., Ph.D., an assistant professor of laboratory medicine at UCSF and director of the UCSF-Abbott Viral Diagnostics and Discovery Center, who spearheaded the UCSF effort to identify the virus. Dr. Chiu and his team continue to work on new diagnostics to detect the virus so that health officials in the Congo and elsewhere can quickly identify it should it emerge again. One odd characteristic of the Bas-Congo virus, Dr.