Killing Brain Tumors From Within: A 'Trojan Horse' Approach

[Cathya]

Killing Brain Tumors From Within: A 'Trojan Horse' Approach

A new method for targeting malignant brain tumors through inducing the cancerous cells to "commit suicide" has been developed by a team of researchers headed by a Hebrew University of Jerusalem professor of biochemistry.



Alexander Levitzki, who is the Wolfson Family Professor of Biochemistry, his research associate, Dr. Alexei Shir, and his colleagues from the Ludwig-Maximilians University of Munich, Germany, have pioneered a technique in which a molecule containing long, double-stranded RNA is attached to epidermal growth factor (EGF) and delivered selectively to cells with an abnormally high number of epidermal growth factor receptors (EGFR).

This proliferation of EGFR is typical of certain types of cancer cells, including glioblastoma multiforme (GBM), the most lethal form of brain cancer.

The nucleic acid-EFG molecule acts as a "guided missile," explained Prof. Levitzki, which, when injected into the blood stream, is avidly gobbled up by the multiple EGF receptors on the cancer cells, without harming normal cells. Once embedded in the tumor cells, it destroys them from within -- a true "Trojan horse," said Prof. Levitzki. Normal cells, which possess 20 to100 less receptors for EGF, are spared, since the amount of double-stranded RNA gobbled up is insufficient to induce them to die.

The lethal RNA approach has been applied to mice in which human brain tumors were grown. The tests proved 100% effective in eliminating the tumorous growths.

An article on the work of Prof. Levitzki, along with his associate Dr. Shir and Professors Manfred Orgris and Ernst Wagner of Ludwig-Maximilians University in Munich, was published in a recent article in the journal PLOS Medicine.

Further testing is planned in a clinical setting. In the meantime, a small start-up company, Algen Biopharmaceuticals Ltd., has been established through the Hebrew University's Yissum Technology Transfer Company to promote commercial development of the new drug. Prof. Levitzki believes that the project has great potential, especially in view of the fact that over-expression of EGF receptors is involved in over 25 % of all types of cancers. The strategy developed to combat GBM can also be applied to other types of receptors found on cancerous cells, he added.

Last year, Prof. Levitzki was named as a winner of the prestigious Wolf Prize in Medicine for his research on cancer development and treatment. His previous work has already led to successful therapy in treating leukemia and some lung cancer patients.

[Tom]

Now THIS is exciting stuff. But I can't help wonder how bittersweet the day will be when there is a true cure for this crap. The memories of all those we loved that weren't here to benefit will haunt me I suspect. We shall see, and I think it might be sooner than we all think.

[eric]

From your mouth to God's ears Tom. Too many wonderful people have already been lost.

[Lani]

very few breast cancers Overexpress EGFR, compared to the many which overexpress her2..but with a little modification of this technique...

1: PLoS Med. 2006 Jan;3(1):e6. Epub 2005 Dec 6. Links
EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice.

Shir A,
Ogris M,
Wagner E,
Levitzki A.
Department of Biological Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
BACKGROUND: Glioblastoma multiforme (GBM) is the most lethal form of brain cancer. With the available treatments, survival does not exceed 12-14 mo from the time of diagnosis. We describe a novel strategy to selectively induce the death of glioblastoma cells and other cancer cells that over-express the EGF receptor. Using a non-viral delivery vector that homes to the EGF receptor, we target synthetic anti-proliferative dsRNA (polyinosine-cytosine [poly IC]), a strong activator of apoptosis, selectively to cancer cells. METHODS AND FINDINGS: Poly IC was delivered by means of a non-viral vector: 25kDa polyethylenimine-polyethyleneglycol-EGF (PEI25-PEG-EGF). EGFR-targeted poly IC induced rapid apoptosis in the target cells in vitro and in vivo. Expression of several cytokines and "bystander killing" of untransfected tumor cells was detected in vitro and in vivo. Intra-tumoral delivery of the EGFR-targeted poly IC induced the complete regression of pre-established intracranial tumors in nude mice, with no obvious adverse toxic effects on normal brain tissue. A year after treatment completion the treated mice remain cancer-free and healthy. Similarly, non-viral delivery of poly IC completely eliminated pre-established breast cancer and adenocarcinoma xenografts derived from EGFR over-expressing cancer cell lines, suggesting that the strategy is applicable to other EGFR-over-expressing tumors. CONCLUSION: The strategy described has yielded an effective treatment of EGFR over-expressing GBM in an animal model. If this strategy is translated successfully to the clinical setting, it may actually offer help to GBM patients. Moreover the elimination of two additional EGFR over-expressing cancers in vivo suggests that in principle this strategy can be applied to treat other tumors that over-express EGFR.
PMID: 16318410 [PubMed - in process]