Cancer Cells Persuaded to Self-Destruct

A method has been developed to destroy cancer cells without damage to surrounding normal tissue through activation of double-stranded RNA (dsRNA)–dependent protein kinase (PKR), a potent growth inhibitory protein that is primarily activated in virally infected cells. The method was described August 19, 2002, in the online edition of Nature Biotechnology.

PKR is activated as a result of viral invasion of normal cells. The activated protein triggers a process that results in death of the cell. Researchers at the Hebrew University of Jerusalem (Israel) developed a technique for inducing cancer cells that express mutated genes containing deletions or chromosomal translocations to activate PKR without activating it in normal cells. They found that antisense (AS) RNA complementary to fragments flanking the deletion or translocation could produce a dsRNA molecule of sufficient length (39-nucleotides) to activate PKR and induce cell death following hybridization with mutated but not wild-type mRNA.

This in vitro study was followed by experiments in mice with brain tumors. A lentiviral vector expressing the 39-nt AS sequence was found to strongly inhibit glioblastoma growth in mouse brain when injected after tumor cell implantation.

Professor Alex Levitzki of the department of biological chemistry of the Hebrew University cautioned that a great deal of laboratory and clinical work remains to be done before this technique will be able to be implemented in treatment of cancer patients.




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Hebrew University of Jerusalem