Exploring the impact of anti-oestrogen resistance on the capacity of breast cancer cells to modulate bone cell function

Project background: Around 50,000 breast cancers are diagnosed each year in the UK. Although endocrine therapies designed to inhibit estrogen receptor signalling have been of great benefit to breast cancer patients, acquired resistance to such agents occurs in over a third of breast cancers and thus represents a significant clinical problem particularly since relapsed tumours frequently present as bone metastases. Our recent cell model data provides evidence supporting a link between acquired resistance and the overexpression of a number of bone-regulatory growth factors. Subsequently, resistant breast cancer cells are able to induce bone cell precursor differentiation in vitro.

Hypothesis and aims: Our hypothesis is that acquisition of resistance to endocrine therapies in breast cancer influences their ability to cross-talk with bone cells in a manner that promotes (i) differentiation of bone cell precursors into osteoclasts with subsequent bone destruction and (ii) osteoclast-mediated release of growth factors within the bone that stimulate growth of the tumour itself.
This PhD will investigate this hypothesis, exploring further how anti-oestrogen resistance alters the capacity of breast cancer cells to influence bone cell behaviour and elucidating the role of specific intracellular kinases in this process with a view to their potential identification as therapeutic target(s) through which bone metastasis might be suppressed.


This studentship is a great opportunity to join Dr Hiscox’s active and successful multidisciplinary research team in the School of Pharmacy and Pharmaceutical Sciences (http://www.cardiff.ac.uk/phrmy/contactsandpeople/fulltimeacademicstaff/hiscox-stevenew.html) which focused is on the mechanisms underlying drug response and resistance in breast cancer and applying this knowledge to develop new, and improve existing, treatments. An extensive range of research facilities are available including a microscopy suite, flow cytometer, histology facilities, independent prokaryotic growth labs and a dedicated eukaryotic culture laboratory and full equipment for molecular and cellular biology. This project will be run in close collaboration with Dr Bronwen Evans (School of Medicine; http://medicine.cf.ac.uk/person/dr-bronwen-alice-james-evans/) who has expertise in bone cell function and signalling analysis. PhD students are supported by the presence of a number of expert technical staff and the School has a thriving post-graduate community which will provide an exciting and stimulating environment for research training.