Background
The focus of the work the Biochemistry Department is on the >75% of breast cancer which presents as ER+ disease. In these cases endocrine therapy is considered mandatory. When given as adjuvant therapy tamoxifen reduces the odds of recurrence in ER+ disease by 41% and aromatase inhibitors (AIs) improve this by about another proportional 20-30%. It is likely that tamoxifen and oestrogen deprivation will remain the foundation of endocrine therapy for the foreseeable future.
Despite the undoubted value of these drugs, some patients show intrinsic resistance and others acquire resistance to them. Although many new targeted agents in development might be useful in combination or sequence with endocrine therapy there is little data on the mechanisms of endocrine response or resistance that can direct their appropriate use.
Our aim
The Translational Research team is based within the Royal Marsden Hospital-ICR Academic Department of Biochemistry. Our aim is to conduct biochemical analyses to identify mechanisms of response and resistance to anti-hormone therapies. By doing so, we will be able to identify markers that can be used to select patients for the most appropriate treatment and new targets for treatment that should avoid the development of resistance and/or treat the resistant disease.
Our research
We are assessing changes in the expression of thousands of genes in the tumours of patients being treated with aromatase inhibitors, and also identifying gene losses and gains in tumours that predispose them to resistance to endocrine treatment.
About 25-40% of patients that relapse during tamoxifen therapy having lost expression of the oestrogen receptor; we will conduct analyses of sets of such tumours to determine the mechanism and implications of this fundamental molecular change.
