Blocking gene opens avenues for treating prostate cancer

Cancer Research UK scientists in Oxford have found a new way to make prostate cancer succumb more readily to currently used treatments.

Prostate cancer is resistant to most forms of chemotherapy and is notoriously difficult to treat.

But in a new study published today (Friday) (note 1), researchers report that blocking the action of a gene called IGF1R (note 2) can make prostate cancer cells more sensitive to radiotherapy and certain kinds of chemotherapy.

The team has high hopes the technique could improve survival prospects for patients with prostate cancer that has become resistant to treatment.

Dr Val Macaulay, Cancer Research UK Senior Clinical Research Fellow at the Weatherall Institute of Molecular Medicine in Oxford, explains:

"One of the most effective ways of treating prostate cancer is to starve it of the male hormones that feed it in its early stages. But at some point these cancers always become hormone independent and this form of treatment ceases to work.

"Prostate cancer is also resistant to most chemotherapy drugs so there is an urgent need for new ways to tackle the disease."

Previous work had shown that IGF1R might be a good target for cancer treatment, and inhibitors of the gene are currently being developed. The team set out specifically to see if inactivating the gene could improve the impact of existing treatments on prostate cancer.

They used a new technology called RNA interference (RNAi) to block IGF1R. RNAi has the unique ability to switch off a single one of a cell's 35,000 genes.

Switching off IGF1R in a selection of prostate cancer cells resistant to different treatments made the cells two times more sensitive to radiotherapy.

"We also found that blocking the IGF1R gene enhanced the effect of chemotherapy on hormone independent prostate cancer cells, so this technique could be effective against prostate cancers that are resistant to hormone-based therapy," Dr Macaulay adds.

The technique made the cells significantly more sensitive to chemotherapy drugs that kill cells by damaging their DNA. In contrast, the technique did not enhance the effect of chemotherapy drugs that kill without causing DNA damage.

Dr Macaulay says: "These results suggest that IGF1R plays a role in the cell's response to DNA damage, and will tell doctors which type of chemotherapy drugs are likely to be enhanced by treatments targeting the gene.