EGFR inhibitors have the potential to decrease the dispersal potential of circulating tumour cell clusters

Most cancer-related deaths are due to the spread of tumour cells throughout the body - a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can be found as either single cells or clusters of cells (often including platelets), with the latter having the highest metastatic potential. However, the biology of CTC clusters is not well understood and there are no therapies that specifically target them. We previously developed an in vitro model-system for CTC clusters and proposed a new extravasation model that involves cluster dissociation, adherence and single-cell invasion in response to TGF-B1 released by platelets. Here, we investigated TGF-B1-induced gene expression changes in our CTC cluster-like cell line, focusing on genes for which targeted drugs are available. In addition to the upregulation of the TGF-B1 signalling pathway, we found that: (i) genes in the EGF/EGFR pathway, including those coding for EGFR and several EGFR ligands, were also induced, and (ii) Erlotinib and Osimertinib - two EGFR/tyrosine kinase inhibitor drugs, decreased the TGF-B1-induced adherence and invasion of the CTC cluster-like line. Overall, we argue that EGFR inhibitors can be used to decrease the dispersal potential of CTC clusters and improve patient survival.