Amplification of multiple cell-growth genes found in some brain tumors. A small percentage of the deadly brain tumors called glioblastomas, which usually resist treatment with drugs targeting mutations in cell-growth genes, appears to contain extra copies of two or three of these genes at the same time. The surprising discovery by a Massachusetts General Hospital (MGH)-based research team has major implications for the understanding of tumor biology -- including the evolution of tumor cell populations -- and for targeted cancer therapies. "We found that about 5 percent of glioblastomas contain amplification of multiple receptor tyrosine kinase genes -- specifically EGFR, MET and PDGFA -- in intermingled mosaic subpopulations of cells," says John Iafrate, MD, PhD, of the MGH Department of Pathology and MGH Cancer Center, corresponding author of the report appearing in the Dec. 13 issue of Cancer Cell. Matija Snuderl, MD, and Ladan Fazlollai, MD, of the MGH Department of Pathology are co-lead authors of the Cancer Cell article.
Old drugs find new target for treating brain tumor. Scientists at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center, in collaboration with colleagues in Boston and South Korea, say they have identified a novel gene mutation that causes at least one form of glioblastoma (GBM), the most common type of malignant brain tumor. The findings are reported in the online edition of the journal Cancer Research. Perhaps more importantly, the researchers found that two drugs already being used to treat other forms of cancer effectively prolonged the survival of mice modeling this particular form of GBM. That could be good news for at least some GBM patients.
More than 9,000 new cases of the disease are diagnosed each year in the United States and effective treatments are limited. The tumors are aggressive and resistant to current therapies, such as surgery, radiation and chemotherapy. The median survival rate for newly diagnosed GBM patients is just 14 months. Mechanism in brain cancer responsible for neuron death discovered. Researchers from Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicinehave discovered a mechanism by which glioblastoma multiforme (GBM), the most common form of brain cancer, promotes the loss of function or death of neurons, a process known as neurodegeneration. The findings could lead to new therapies that suppress neurodegeneration caused by GBM and, potentially, a variety of other neurodegenerative diseases.
The study, recently published in the journal Cancer Research, was led by Paul B. This study is the first of its kind in that it provides a direct mechanistic link between GBM, neurodegeneration and glutamate transport and explains a process by which GBM, through expression of the AEG-1 oncogene, can provoke the death of neurons.
AEG-1 was originally cloned in Fisher's laboratory and is overexpressed in more than 90 percent of all brain tumors. Fisher collaborated on this study with Keetae Kim, Ph.D., Timothy P. New oncolytic virus shows improved effectiveness in preclinical testing. A new fourth-generation oncolytic virus designed to both kill cancer cells and inhibit blood-vessel growth has shown greater effectiveness than earlier versions when tested in animal models of human brain cancer. Researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) are developing the oncolytic virus as a treatment for glioblastoma, the most common and deadly form of brain cancer (average survival: 15 months after diagnosis).
The new oncolytic virus, called 34.5ENVE, improved survival of mice with transplanted human glioblastoma tumors by 50 percent in a majority of cases compared with the previous-generation oncolytic virus. The study was published online in the journal Molecular Therapy. "These findings show the amazing therapeutic efficacy of this new oncolytic virus against four different glioblastoma models in animals," says cancer researcher Dr. Researchers Find Coupling of Proteins Promotes Glioblastoma Development. Previously unknown role of FoxM1 is crucial to regulation of brain tumor stem cells MD Anderson News Release 10/21/11 Two previously unassociated proteins known to be overly active in a variety of cancers bind together to ignite and sustain malignant brain tumors, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports this week in the journal Cancer Cell.
This research is the first to connect FoxM1 to a molecular signaling cascade that regulates normal neural stem cells, said senior author, Suyun Huang, M.D., Ph.D., associate professor in MD Anderson's Department of Neurosurgery. "When FoxM1 binds to beta-catenin, we found that it also supports the self-renewal and differentiation of glioma- initiating cells, cancer stem cells thought to drive glioblastoma multiforme," Huang said. Glioblastoma multiforme is the most common and lethal form of brain tumor. Protein's connection could be drug target Blocking FoxM1 reduces glioblastoma in mice 100 percent. New way to screen for brain cancer stem cell killers. Researchers with UCLA's Jonsson Comprehensive Cancer Center have developed and used a high-throughput molecular screening approach that identifies and characterizes chemical compounds that can target the stem cells that are responsible for creating deadly brain tumors.
Glioblastoma is one of the deadliest malignancies, typically killing patients within 12 to 18 months. These brain cancers consist of two kinds of cells, a larger, heterogeneous population of tumor cells and a smaller sub-population of stem cells, which are treatment-resistant. The screening system was specifically designed to find drugs that can target that sub-population and prevent it from re-seeding the brain cancer, said study senior author Dr. Harley Kornblum, a Jonsson Cancer Center scientist and a professor of psychiatry and biobehavioral sciences. The study appears in the Oct. 10 issue of Molecular Cancer Therapeutics, a peer-reviewed journal of the American Association of Cancer Research.
Nanoparticles seek and destroy glioblastoma in mice. Targeting Cholesterol to Fight Deadly Brain Cancers. Blocking the uptake of large amounts of cholesterol into brain cancer cells could provide a new strategy to battle glioblastoma, one of the most deadly malignancies, researchers at UCLA’s Jonsson Comprehensive Cancer Center have found. The study, done in cells lines, mouse models and analysis of tissue from brain cancer patients, uncovered a novel mechanism by which the most commonly activated oncogene, the mutated epidermal growth factor receptor (EGFR), overcomes normal cell regulatory mechanisms to feed large amounts of cholesterol to the brain cancer cells, said Dr. Paul Mischel, a professor of pathology and laboratory medicine and molecular and medical pharmacology, a Jonsson Cancer Center researcher and senior author of the study.
The study appears Sept. 15 in Cancer Discovery, the newest peer-reviewed journal of the American Association for Cancer Research. “That was a surprise here, this ghastly trick of the cancer cells,” Mischel said. Comment/Share.