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 study1, researchers report that blocking the action of a gene called IGF1R2 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.
“This is the first study to show that silencing the IGF1R gene can improve the effectiveness of treatments for prostate cancer. As an oncologist I am excited at the possibility of conducting trials of IGF1R-inhibiting drugs with my own patients.”
Professor Robert Souhami, Director of Policy and Communication at Cancer Research UK, says: “Cancer cells have broken free of natural controls over their ability to divide. Many researchers are looking at ways to bring cancer cells back under control and to stop them dividing and spreading around the body.
“IGF1R sustains many types of cancer cell, so blocking the gene could prove a powerful new way of treating tumours. This is early stage research, but holds great promise in the fight against not only prostate cancer but other forms of the disease.”
- Cancer Gene Therapy
- Type 1 insulin-like growth factor receptor
The IGF1R gene is overactive in prostate cancer cells. It allows the cells to cheat death and helps prostate tumours grow.
A number of molecules designed to impede IGF1R are already being developed by pharmaceutical companies.
RNAi was discovered in the nematode worm, which uses the process to switch off rogue genes that would otherwise cause it harm. Scientists have developed RNAi to enable them to block individual genes experimentally.
RNAi uses small molecules to stand in the way of specific genes to stop them working. Cancer scientists use the technique to disable genes that have ceased working properly and are causing or sustaining cancer.
Chemotherapy drugs used in the study:
- The drugs that kill cells by damaging their DNA were mitoxantrone, etoposide and nitrogen mustard.
- The drugs that kill without causing DNA damage were paclitaxel and 5-fluorouracil.