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Preclinical study of a new brain tumor therapy

PLOS

Scientists have devised a strategy to treat tumors by selectively targeting and killing the malignant cells. A new preclinical study, published in the open access journal PLoS Medicine, has applied the approach to combat glioblastoma multiforme (GBM). This is the most aggressive form of brain tumour, growing very quickly before symptoms are experienced and killing most patients within a year of diagnosis.

Working in mice, Alexander Levitzki and colleagues (of The Hebrew University of Jerusalem and Ludwig-Maximilians-University in Munich) took advantage of previous research that showed how to distinguish between cancerous and healthy cells through the detection of molecules known as epidermal growth factor receptors (EGFR). The glioblastoma cells overexpress EGFR (that is, in comparison with normal brain cells, they have many more of these molecules on their surface). The scientists then selected a type of genetic material (a nucleic acid) associated with viral infections and linked it to a compound that could bind to EGFR. As a result of the defence mechanisms that have evolved to protect mammalian cells from viruses, cells are programmed to die once they take up this particular nucleic acid. The treatment therefore eliminates the tumor cells but avoids damage to the normal brain tissue.

The researchers found that the treatment was effective in mice implanted with human brain tumor cells that overexpressed EGFR. The treatment could eliminate established cancers and there was no evidence of recurrence: the mice remained cancer free for over a year. It is more difficult to cure cancer in humans than cancer in mice, but the results are encouraging. In his Perspective article accompanying the study, Robert Weil of the Brain Tumor Institute at the Cleveland Clinic Foundation suggests that the approach deserves to be "fast-tracked to the clinic" given the lack of effective treatments for GBM. There are few existing options aside from chemotherapy and surgery to remove the tumor, and it is rare that these treatments stop the cancer from recurring. Given the prevalence of EGFR in cells of other cancer types (such as breast cancer and lung cancer), the approach pioneered in this study may be applicable to other forms of cancer as well.

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Citation: Shir A, Ogris M, Wagner E, Levitzki A (2006) EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLoS Med 3(1): e6.

On the related Perspective article: Citation: Weil RJ (2006) Glioblastoma multiforme--Treating a deadly tumor with both strands of RNA. PLoS Med 3(1): e31.

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-01-weil.pdf

CONTACT: Alexander Levitzki
The Institute for Advanced Studies
The Hebrew University of Jerusalem
Jerusalem, Israel 91904
+972-2-6585-404
+972-2-6512-958 (fax)
levitzki@vms.huji.ac.il

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