A WAY of targeting and killing tumour cells with specific mutations could lead to new treatments for many cancers.
The method is a twist on the 鈥渁ntisense鈥� treatments already being tested against cancer. Here, the idea is to turn off a gene by introducing antisense RNA strands that bind to and block the mRNA blueprints for making the protein.
The problem is that turning off a gene doesn鈥檛 always kill cancer cells. But when antisense RNA binds to form double-stranded segments over 30 base pairs long, it triggers a viral defence mechanism that results in cell suicide. Alexander Levitzki at the Hebrew University of Jerusalem realised that this could be exploited to target cancer cells.
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If the antisense RNA spans deleted or rearranged genes, such as are found in many cancers, it will bind to form a long double-stranded segment. But in normal cells, only short segments of double-stranded RNA will form. The beauty of the approach is that, unlike antisense drugs, it will kill cancer cells even if the targeted gene isn鈥檛 crucial to their survival.
To test the method, Levitzki鈥檚 team created viruses that insert antisense RNA into cells. The RNA they used spans a deletion found in over 70 per cent of the aggressive brain tumours called glioblastomas. The team injected glioblastoma cells into mice brains. Three days later, they injected the viruses into the tumours. Normal cells were unaffected, but the tumours shrank 40-fold compared with controls, they report in Nature Biotechnology (DOI: 10.1038/nbt730).
The approach could work for a range of cancers, but the particular mutation would have to be identified in each patient before treatment. But the main challenge will be finding an efficient way to deliver the antisense RNA to people, where glioblastoma cells are interspersed with healthy tissue rather than confined to discrete balls as in the mice. 鈥淒elivery is the major hurdle here,鈥� says Howard Fine of the National Cancer Institute in Bethesda.