Cancer breakthrough for UQ researchers

University of Queensland researchers have reported spectacular success in killing cervical cancer cells and preventing the cancer in female mice, using RNA-interference (RNAi) therapy.

The 'designer' RNA molecule targets two genes in the human papilloma virus (HPV), the agent of genital herpes and the trigger for cervical cancer.

Molecular virologist Dr Nigel McMillan, who headed the project at the Centre for Immunology and Cancer Research at the Princess Alexandra Hospital, said the molecule appears to be "exquisitely specific" in inducing apoptosis - programmed cell death - in HPV-infected cells lining the cervix.

McMillan said the advance was a world first - his team has published its findings in the current issue the international journal Molecular Pharmacology.

"We have shown that we can take cervical tumour cells, treat them with the RNAi agent, put them into mice, and they don't develop cervical cancer," he said.

"One of the target HPV genes, E6, binds to the retinoblastoma oncogene, causing it to be over-expressed, and triggering uncontrolled growth and replication in infected cells

The other HPV gene, E6, produces a molecule that binds to the P53 tumor-suppressor protein, preventing infected cells undergoing apoptosis, and effectively immortalizing them. McMillan said the two viral genes effectively sent infected cells into overdrive, while disabling their brakes.

The beauty of the RNAi molecule's "twin target" approach is that it specifically targets viral genes with no homologue in normal human cells, so there it is harmless to normal, healthy cervical cells, even at very high concentrations.

It was equally effective in triggering apoptosis in cervical cancer cells infected by other sub-types of HPV.

McMillan said human trials were at least three years away. "We need an effective delivery system to deliver the RNAi molecule to cervical tumours in vivo. "We also need to ensure the reagent is as specific as we believe it to be," he said.

It might be possible to deliver the RNAi therapeutic via a lentivirus, which would integrate into cancerous cells and kill them, or to use a synthetic delivery system.

McMillan said around 300,000 Australian women a year return an abnormal result from their pap smear tests. A small RNAi molecule, applied to the cervix as a topical gel, would work for pre-cancerous lesions or early-stage cancers, but a synthetic system such as 'stealth liposomes' might be necessary to treat more advanced cancers .