Fighting resistant breast cancer

There is new hope in the fight against resistant forms of breast cancer as Griffith HealthInstitute (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. In2009, breast cancer was the most common cancer in Australian women (excluding nonmelanomaskin 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 beinefficient 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 aimingto target these resistant forms of the disease with a modified version of tamoxifen, whichcauses accumulation of the anti-cancer agent in mitochondria, the powerhouse of thecell.

Anti-cancer agents that act on mitochondria

This new compound, called MitoTAM, is a member of the group of mitocans, anti-canceragents 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 MitoTAMtreatment at a 10 times lower dose, compared to tamoxifen,” says Professor Neuzil, whois presenting his research at this year’s Gold Coast Health and Medical ResearchConference 2013.

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

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

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

“Plus there are many HER2-high patients who have been found to be resistant toHerceptin. 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 forHER2-high breast cancer patients.