Blood exosomes shown to contain tumor-specific genetic information for brain cancer
King Pharmaceuticals, Inc. and Alpharma Inc. have announced that the two companies have signed a definitive merger agreement under which King will acquire all of the outstanding shares of Class A Common Stock of Alpharma for $37.00 per share in cash for a total equity value of approximately $1.6 billion. The Boards of Directors of
Full Post: King Pharmaceuticals and Alpharma sign definitive merger agreement
Tiny vesicles called exosomes released into the bloodstream from aggressive brain tumors contain genetic signatures that may help guide future diagnosis and treatment of this deadly disease.
In their report in the December issue of Nature Cell Biology (DOI: 10.1038/ncb1800), Massachusetts General Hospital researchers describe finding tumor-associated gene messages in the blood samples of brain cancer patients, including the gene mutation known as EGFRvIII, which is specific for the aggressive form of brain cancer glioblastoma.
“The fact that we can harvest this important cancer signature from exosomes circulating in blood is a critical demonstration of Exosome’s technology for advanced personalized medicine diagnostics”, said James R. McCullough, chief executive officer of Exosome Diagnostics. “Exosomes offer us the possibility of diagnosing and monitoring a variety of cancers from blood draws, rather than solely by invasive tissue biopsies. In addition, because the effects of some anti-cancer drugs are enhanced or disabled by a tumor’s genetic composition, it may be possible to manage treatment regimens by analyzing the genetic contents of patient exosomes.”
Exosome Diagnostics is developing several tests using the non-invasive exosome technology to measure single genetic mutations such as those found in the EGFR, KRAS and BRAF genes for use in lung, colon, brain and melanoma cancers. The Company is also developing complex mutational profiles of cancer tumors for monitoring disease progression and mutational status. After the research described in the paper was completed, Exosome Diagnostics exclusively licensed Massachusetts General Hospital’s provisional patent on the technology.
“We believe these results have broad implications for personalized medicine,” said Johan Skog, Ph.D., director of genetics at Exosome Diagnostics. “Detecting mutational profiles through a noninvasive blood test could allow us to monitor how a tumor’s genetic makeup changes in response to therapy, which may necessitate changes in treatment strategy.” The lead author on the study, Dr. Skog, is also with the MGH Neuroscience Center.
Many types of cells release exosomes as part of normal cell-to-cell communication, and several types of tumor cells are known to shed exosomes containing proteins that can alter the cellular environment to favor tumor growth. The current investigation is believed to be the first to carefully analyze the contents of exosomes shed from glioblastoma cells and to characterize their genetic content.
“Because they contain virtually the entire transcriptome,” said Dr. Skog, “exosomes may one day be used to conduct full tumor genetic profiling to help with early diagnosis and eligibility for personalized therapeutic treatment based on an individual’s specific tumor.”
The investigators first analyzed tumor cells from three glioblastomas and verified that the cells released exosomes containing RNA and protein molecules, sometimes at levels significantly different from that present in the tumor cells themselves. Some messenger RNAs related to activities such as cell proliferation and migration, angiogenesis or immune response were highly abundant in the exosomes but not in tumor cells from the same patient. When labeled glioblastoma exosomes were cultured with normal cells, tumor RNA was delivered into the normal cells and translated into proteins.
To study the potential of glioblastoma exosomes as markers of a tumor’s genetic makeup, the research team analyzed tumor tissue and blood serum from 25 glioblastoma patients and were able both to find tumor exosomes and to identify, in some samples, a mutation in the epidermal growth factor receptor (EGFR) gene that characterizes a tumor subtype. In two patients, exosome analysis identified an EGFR mutation that did not appear in the sample of tumor tissue, reflecting how the often-chaotic diversity of cells within a tumor may cause a surgical biopsy to miss cells carrying critical information.
Xandra Breakefield, PhD, of the MGH Neuroscience Center is the senior and corresponding author of the Nature Cell Biology paper. She is also a member of the Exosome Diagnostics scientific advisory board. Additional co-authors are Tom Wurdinger, PhD, Sjoerd van Rijn, Dimphna Meijer, Laura Gainche, and Miguel Sena-Esteves, PhD, MGH Neuroscience Center; William Curry Jr, MD, and Robert Carter, MD, PhD., MGH Neurosurgery; and Anna Krichevsky, PhD, Brigham and Women’s Hospital.
Microvesicles - tiny membrane-covered sacs - released from glioblastoma cells contain molecules that may provide data that can guide treatment of the deadly brain tumor. In their report in the December 2008 Nature Cell Biology, which is receiving early online release, Massachusetts General Hospital (MGH) researchers describe finding tumor-associated RNA and proteins in membrane microvesicles called exosomes
Full Post: Microvesicles released from glioblastoma cells carry information that may guide treatment
UC Davis Cancer Center researchers report today the discovery of a molecule that targets glioblastoma, a highly deadly form of cancer. The finding, which is published in the January 2009 issue of the European Journal of Nuclear Medicine and Molecular Imaging , provides hope for effectively treating an incurable cancer. Glioblastoma is the most common
Full Post: Discovery of molecule that targets brain tumors
Working with a nanoparticle designed to target and image glioblastoma, a form of brain cancer, investigators at the University of Washington in Seattle have found that these same nanoparticles inhibit tumor cell invasion, one of the key events that leads to the metastatic spread of cancer. The investigators have also determined how the nanoparticles exert
Full Post: Toxin-nanoparticle combo inhibits brain cancer invasion while imaging tumors
Researchers at Georgetown University Medical Center have found a gene they say is inactivated in two aggressive cancers - malignant melanoma, a form of skin cancer, and glioblastoma multiforme, a lethal brain tumor. They add that because this gene, known as PTPRD, has recently been found to be inactivated in several other cancers as well,
Full Post: GUMC researchers find gene inactivated in two aggressive cancers
The metastasis or spread of breast cancer to other tissues in the body can be predicted more accurately by examining subnetworks of gene expression patterns in a patient’s tumor, than by conventional gene expression microarrays, according to a presentation at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17, 2008 in San
Full Post: Gene subnetworks provide new prognostic markers for breast cancer