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Gene-blocking injection halts breast cancer progression in mice

6 January 2014
Appeared in BioNews 736

An injection to prevent breast cancer by silencing a cancer-causing gene has shown early promise in mouse studies.

Professor Don Ingber of Harvard Medical School, one of the lead authors of the paper, said: 'The findings open up the possibility of someday treating patients who have a genetic propensity for cancer, which could change people's lives and alleviate great anxiety'.

Advances in screening have meant that doctors can now identify breast tissue at risk of becoming cancerous. But treatment remains limited to either surgery or regular monitoring to see if the tissue progresses into more advanced cancer. If it does, chemo- and radio-therapy can both have severe side effects and are not guaranteed cures.

The aim of researchers at Harvard University's Wyss Institute is to develop more reliable therapies by identifying genes important in cancer development, and then stopping them before they cause tumours to develop.

However, finding single cancer-causing genes is difficult as genes rarely work alone, but instead form large gene networks. To overcome this problem, researchers used a computer model to 'reverse-engineer' the gene networks in ductal carcinoma in situ (DCIS) - an early form of breast cancer where cancerous cells are seen in the milk-ducts in the breast, but have not spread to other breast tissue.

After initially earmarking over 100 genes, the scientists eventually concentrated on just one, HoxA1, which seemed to drive breast cancer formation.

By using small interfering RNA (siRNA) to 'turn-off' HoxA1, they were able to stop cancerous cells in culture from over-growing, and instead start acting like healthy breast cells.

This siRNA, packaged in specialised nanoparticles, was then injected directly into the milk-ducts of mice that had been genetically engineered to develop DCIS-like tumours. While all untreated mice developed cancer, 75 percent of those given the treatment remained cancer-free several weeks later.

The siRNA would need years of testing and fine-tuning before it could ever be used in humans. But the researchers' goal is to develop a non-surgical treatment for patients with early-stage breast cancer or people at high genetic risk of developing the disease.

'The idea would be start giving it early on and sustain treatment throughout life to prevent cancer development or progression', said Professor Ingber.

Speaking to the Daily Mail, Dr Kat Arney of Cancer Research UK, said the study revealed 'an exciting new approach, although it's important to remember that it's only been done in mice so far and is still highly experimental'.

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