Breast Cancer (Molecular Pharmacology) Group, School of Pharmacy & Pharmacuetical Sciences, Cardiff University, Cardiff CF10 3NB, United Kingdom
Historically our group (previously Tenovus Centre for Cancer Research) has undertaken research in the area of anti-hormone and anti-growth factor resistance in breast cancer through signal transduction/pharmacological challenge studies. Two of our key current research interests are (i) exploring very early anti-hormone-induced "compensatory" signal transduction that limits initial response, promotes cell survival and facilitates evolution of resistance and further features of progression (e.g. invasion). (ii) modelling and deciphering of signalling pathways altered as a consequence of long-term (>3yr) adjuvant antihormone exposure (versus initial acquired resistance). A pervading goal in all our studies is to reveal new therapeutic targets to subvert resistance/progression and improve response, as well as providing new markers of therapeutic response & prognosis.
Cell culture and signal transduction methodologies (including Western Blotting/PCR/reporter gene construct assays, pharmacological/antibody challenge) are core for candidate pathway studies as applied to our breast cancer models. My own areas of expertise lie in immunocytochemistry, notably using phosphospecific antibodies and their application to clinical material. I have also recently coordinated Affymetrix microarray studies as applied to our panel of cell lines that are revealing novel signalling elements induced during early drug treatment or elevated in established resistance. The relevance of these changes is subsequently being explored through functional studies, including employing SiRNA knockdown.
In house panel of in vitro models derived from anti-hormone responsive ER+ HER2- and ER+ HER2+ breast cancer cells to reflect acquired resistance to various antihormones and erbB inhibitors, such as herceptin. Our recent studies extend into 3D cell culture.