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An international team of researchers including Pernette Verschure and PhD student Mannus Kempe from the UvA's Swammerdam Institute of Life Sciences has discovered a mechanism that makes a common type of breast cancer cells resistant to a specific form of hormone treatment. Their findings have been published in the latest issue of Nature Genetics.

Activation of the aromatase gene in breast cancer cells that escaped from endocrine therapy. The highlighted circle illustrates the detection of the aromatase gene activity at single molecule resolution level. Credits: Pernette Verschure and Mannus Kempe

Treatments for breast cancer often rely on hormone therapy. When the tumour cells fail to respond to hormone therapies, the patient can develop a metastasised form of breast cancer. The aim of this study was to find out what causes the initial disruption in the post-menopausal hormone treatment (in this case, using aromatase inhibitors). The research was conducted using tumour tissue from patients who had been treated with hormone therapy and undergone a second biopsy. 

The researchers discovered that activation of one specific gene switches on oestrogen production in tumour cells such that the cells stop responding to the hormone therapy and patients develop a metastasic breast cancer.  The UvA researchers managed to microscopically identify the disrupted cells using a method that enables to visualize single cells at resolution level of a few molecules. The findings of the present study suggest an as-yet unknown mechanism is behind the development of early-phase aromatase inhibitor resistance. 

Major breakthrough

The discovery marks a major breakthrough, as the mechanism that enables this type of breast cancer cells (oestrogen-receptor positive) to escape hormone treatment was largely unknown until now. Approximately 70% of diagnosed breast cancer patients have this particular type of breast cancer and most of them receive hormone therapy as follow-up treatment. In more than 20% the cancer returns later on and the patients eventually die of an incurable form of breast cancer. The development of specific biomarkers could make it possible to provide individually tailored treatments, thereby maximising the efficacy of treatment while minimising the side effects.

EpiPredict EU H2020 consortium

This study is part of the research being conducted by EpiPredict, an international consortium funded by a EU Horizon 2020 grant from the Marie Sklodowska Curie Actions programme for research and innovation. EpiPredict research takes a 'systems medicine' approach to understanding epigenetic regulation of the development of breast cancer hormone treatment resistance. EpiPredict is an initiative of Dr. Pernette Verschure, associate professor at the Swammerdam Institute of Life Science, she also coordinates the EpiPredict consortium.

The EpiPredict project is made up of fifteen academic and industry institutes across eight different countries, and a group of 12 doctoral researchers, including three at the UvA. In addition to performing scientific research, the doctoral candidates are being trained within the EpiPredict project in areas ranging from academic skills to entrepreneurship and business management, debate and the dissemination of research findings to society.

Publication details

Luca Magnani, Gianmaria Frigè, Raffaella Maria Gadaleta, Giacomo Corleone, Sonia Fabris, Mannus H Kempe, Pernette J Verschure, Iros Barozzi, Valentina Vircillo, Sung-Pil Hong, Ylenia Perone, Massimo Saini, Andreas Trumpp, Giuseppe Viale, Antonino Neri, Simak Ali, Marco Angelo Colleoni, Giancarlo Pruneri & Saverio Minucci: ‘Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERα metastatic breast cancer’ in Nature Genetics, 23 January 2017

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