Fighting resistant breast cancer

There is new hope in the fight against resistant forms of breast cancer as Griffith Health Institute (GHI) research aims to target the disease with novel anti-cancer agents.

Breast cancer occurs when abnormal cells in the breast grow in an uncontrolled way. In 2009, breast cancer was the most common cancer in Australian women (excluding nonmelanoma skin cancer), accounting for 27.4 per cent of all new cancers in women.

Tamoxifen is a potent agent used to treat breast cancers however it is known to be inefficient in treatment of breast tumours with a high level of the oncogene HER2.
Now Professor Jiri Neuzil from GHI’s Molecular Basis of Disease program, is aiming to target these resistant forms of the disease with a modified version of tamoxifen, which causes accumulation of the anti-cancer agent in mitochondria, the powerhouse of the cell.

Anti-cancer agents that act on mitochondria

This new compound, called MitoTAM, is a member of the group of mitocans, anti-cancer agents that act on mitochondria.

“We have been able to chemically alter tamoxifen in such a way that when administered, it will accumulate in the mitochondria of the HER2-high cells and efficiently induce cell

“We have been able to show that HER2-high cells are more sensitive to MitoTAM treatment at a 10 times lower dose, compared to tamoxifen,” says Professor Neuzil, who is presenting his research at this year’s Gold Coast Health and Medical Research Conference 2013.

“We have also observed a remarkable decrease in tumour growth in mice with the MitoTAM treatment, suggesting that it is a very effective anti-cancer agent.”

Professor Neuzil says the research findings could be a real breakthrough for the development of more cost-effective resistant breast cancer treatments.

“Being able to modify tamoxifen in this way provides a much cheaper alternative to other drugs such as Herceptin.

“Plus there are many HER2-high patients who have been found to be resistant to Herceptin. The development of this new experimental drug could provide an alternative to
these people.”

It is hoped that, pending successful pre-clinical testing, there will be MitoTAM trials for HER2-high breast cancer patients.