Aim
The aim of the Molecular Endocrinology team is to characterise the molecular mechanisms associated with resistance to endocrine agents using in vitro systems modelling relapse on tamoxifen or aromatase inhibitors. Our studies focus on alterations in signal transduction pathways and their impact on proliferation, survival, invasion and angiogenesis, each of which is a component of the malignant phenotype.
Overview
Breast cancer is the most common cancer in women in the western world, with approximately 40,000 new cases diagnosed each year in the UK alone. Knowledge that steroid hormones play a pivotal role in the development of breast cancer has been exploited clinically by the development of endocrine treatments (Figure 1). These seek to deprive the hormone dependent tumour cells of oestrogen (E2) by using:
1 aromatase inhibitors which block the conversion of androgens into oestrogens
2 or anti-oestrogens such as the selective oestrogen receptor (ER) modulator tamoxifen, which competes with E2 for the ER.
Unfortunately, the beneficial actions of these endocrine therapies are attenuated by the apparent ability of tumours to circumvent the need for steroid hormones, whilst in most cases, retaining the ER. It is therefore of paramount importance to characterise the molecular mechanisms associated with resistance to endocrine agents.
Our research
Using in vitro systems modeling relapse on endocrine agents, our studies focus on alterations in signal transduction pathways and their impact on proliferation, survival, invasion and angiogenesis, each of which is a component of the malignant phenotype.Using this knowledge we can investigate combination approaches using signal transduction inhibitors in concert with endocrine agents for the treatment of endocrine resistant breast tumours and provide biomarkers that may be used clinically as predictive factors for response to therapy.
