Integrating imaging, exosome and protein network rewiring information to track early tumour evolution of resistance mechanisms

Despite recent advances in developing HER-family targeted drugs, clinical trials have shown poor results. Tumour evolution takes place overtime, frequently leading to aberrant new signalling cascades that disrupt the efficacy of targeted therapies and ultimately cause patients to develop resistance against initially effective drugs. To predict outcome and stratify treatment there is an imperative need to develop a systems understanding of concentration- independent parameters that could be monitored in trials and report on tumour evolution. Amongst the circulating tumour markers, exosomes offer a suitable platform for the longitudinal monitoring of protein network signalling in the form of a liquid-biopsy by imaging receptor dimerisation status. Here, we illustrate the biomarker utility of monitoring oncogenic receptor signal rewiring using exosomal FRET/FLIM to aid the prediction of clinical outcome and patient treatment stratification.