Treating Untreatable Breast Cancers

Treating Untreatable Breast Cancers
Categories: News

breast cancer header

A team led by Alex Swarbrick has suggested that instead of developing drugs designed to treat hard to cure cancers, we must investigate the possibility of changing the cancer itself to a different form and treating that modified cancer with existing medications which are proven to be effective.

Breast cancer is by far the most common cancer amongst women. Approximately 85% of breast cancer tumours rely on the hormones progesterone or oestrogen to grow. Others rely on a protein called HER2. Treatment of HER2 type breast cancer tends to rely on blocking these chemicals so that the growth of cancer cells is inhibited. The alternate type, resistant cancer, is called triple negative cancer and does not require these chemicals to grow.

Some Major Differences

Swarbrick's team at the Garvan Institute of Medical Research in Sydney, Australia, analysed the DNA of 80 women affected by triple negative cancer, looking for differences in their genes. The study showed that the tumours in women with the more aggressive form of cancer produced significant amounts of ID4 protein.

Experiments on mice revealed that ID4 seems to be produced by healthy breast stem cells. This finding suggests that the aggressive form of triple negative breast cancer is a result of a cancerous mutation in a breast stem cell rather than a mutation in a breast tissue cell. Swarbrick suggests that treatment resistant cancers might have developed from stem cells, as stem cells share some of the characteristics of aggressive cancers: they are mobile, adaptable, and less sensitive to damage from radiation.

"We asked, at a whole genome level, what's different? And in fact, they are very different," says Swarbrick. A genome analysis revealed that the two types of tumour, those that produce a lot of ID4 and those that don't, are very different. "They seem to have a completely different history of development. We think they come from a different place."

The next step was to block the production of ID4 protein. In mouse and test-tube models of the disease, when the protein was blocked, tumours stopped growing and a lot of other cancer-related genes in the tumour got changed around. "Suddenly ID4 is acting as a switch, controlling whether a cell is allowed to activate these cancer-related genes," says Swarbrick.

Luckily, the ID4 switched on the genes associated with cancers that respond to oestrogen treatment, making the triple negative cancer easier to treat.

What are the Implications?

"We don't know yet whether we are seeing a real oestrogen-dependent cancer after ID4 is blocked - or just a caricature of one," says Swarbrick. Of course more research will be needed to see how ID4 affects cancer, because other genes also play a role in whether a tumour is susceptible to hormone therapy. The next step is for Swarbrick and his team is to see if the switched tumours respond to the oestrogen-blocking drug, tamoxifen.

The experiments performed opened up a new avenue for treatment of breast cancer. "Maybe we can shift the tumour in the direction of the therapy rather than developing the therapy in the direction of the tumour," says Rob Ramsay from the Peter MacCallum Cancer Centre in Melbourne, Australia.

There are several major implications for the field of oncology if these tests prove successful. Patients could benefit from more accurate information regarding their chance of survival and it may improve targeting of current chemotherapies. However, most importantly, the development of an ID4 blocking drug could allow for a method to treat the most resistant forms of triple negative breast cancer.

"It may offer new treatment opportunities to thousands of women diagnosed with triple negative breast cancer," says Swarbrick.

Leave a Comment