We have particular interests in the receptors belonging to the epidermal growth factor family (HER), since they are critical players in the progression of epithelial neoplasms, including breast, lung, ovarian, colon and pancreatic cancers. Their overexpression is associated with aggressive cancer behaviour and poor patient survival. The invasive tumour biopsies routinely used for the evaluation of receptor status may give an incomplete picture due to sampling errors and tumour heterogeneity. Therefore, one of our research aims focuses on strategies to develop and characterize molecular probes for the non-invasive imaging of HER receptors in vivo. Such an approach will have the advantage of showing receptor expression across the entire tumour and will offer a means of quantifying heterogeneity of protein expression. In addition, the imaging tests can be repeated to monitor temporal changes in receptor level in both unperturbed and treatment-perturbed models. After verification, radiolabelled probes are used for in vivomonitoring/quantification of changes in receptor status following combinations of targeted therapies.
In parallel, we also investigate the downstream components of HER signalling pathways since there are several studies showing that tumours escape HER1- and HER2-targeted therapies by rapid compensatory increase in HER3 expression and the resulting activation of the PI3K/AKT pathway. Recently, multiple oncologic drugs designed to target and disrupt this specific pathway have been developed and it is important to introduce a reliable, functional imaging method to evaluate target inhibition in vivo in order to optimize these therapeutic regimes.