In 2015, we also published an exciting new research that linked cholesterol and breast cancer. Our work was nicely featured as one of the new exciting discoveries from Imperial College.
Patients with breast cancer are commonly divided in oestrogen receptor positive (~70%) and oestrogen receptor negative (~30%). Oestrogen receptor positive patients are treated with endocrine therapies for 5 years after initial surgery. These drugs are designed to block oestrogen receptor activation. Endocrine therapies come in different flavours and typically scientists have studied the development of resistance to these drugs as a common mechanism. In this study, we have found for the first time that the mechanisms of resistance to endocrine therapies are unique to each single agent. Resistance involved epigenetic reprogramming, meaning that cells adapted to each agent using extra-genetic (mutations etc..) mechanism. For example, cells that develop resistance to aromatase inhibitors strongly increase cholesterol production. Aromatase inhibitors are designed to remove oestrogens from the blood thus removing some of the fuel necessary for breast cancer growth. We found that breast cancer cells start refining an alternative fuel source independently and locally (this new fuel is called 27 hydroxyl cholesterol). Using statins (anti-cholesterol) we could partially inhibit some of the invasive phenotypes that evolved in AI resistant cells. More work is needed to translate these findings to the clinic, however, this paper has open the gates to important new developments in breast cancer research. Dr Perone is now following up these data and hopefully will identify practical ways to starve cells from all fuels.