Objective

Drug resistance is currently an inevitable consequence of drug therapy for solid cancers and greater understanding of underlying resistance mechanisms using novel tools that can be translated into the clinical setting to guide treatment selection is critical to improve clinical cancer outcomes. I will describe the impact of an important compensatory/drug resistance mechanism we have formerly termed therapy-induced ErbB/HER/Met receptor tyrosine kinase (RTK) network rewiring; whereby tumors evolve, under treatment pressure, a conformational alteration in ErbB/HER receptor(s) favouring the formation of increased dimerization. The clinically important link to be established is how this process can in turn influence the tumor microenvironment, focusing on unfolded protein response- based mechanisms that can modulate the adaptive and innate immune effectors in the tumour microenvironment. I will also describe the imaging-based tools for monitoring innate immune cells such as innate lymphoid cell class 3 (ILC-3) and S100A9+ myeloid derived suppressor cells, which has added new knowledge to our current understanding of how breast cancers can spread into lymphatics; and how the primary tumour can shed small microvesicles (exosomes) that ‘prime’ distal organs such as the lungs for future metastasis