Ion channels and transporters in breast cancer: promising targets for novel recombinant antibodies

Several types of ion channels are dysregulated in various carcinomas including breast cancer (BCa) and for some of them associations with clinicopathological features have been described. Thus, ion channels could serve as functional biomarkers and be exploited as therapeutic targets in carcinoma management. This appears of particular relevance to those difficult-to-treat cancers, such as ‘triple negative BCa’ (TNBC), characterized by an unfavourable pathophysiology and lack of functional biomarkers. In the present study, we found that two of the ion channels mostly dysregulated in carcinomas, KV11.1 and the neonatal form of NaV1.5 (nNaV1.5), are co-expressed in BCa cells of different molecular subtypes, in particular in TNBC. The two channels control cell motility and invasiveness of TNBC cells. The two channels form a macromolecular complex with the β1 subunit of integrin adhesion receptors and differentially modulate F-actin dynamics. The KV11.1-nNaV1.5-β1 integrin (KNB) complex is also expressed in human primary BCa samples of different molecular subtypes and associates negatively with survival. Specifically, KV11.1 has been demonstrated to be a powerful biomarker for diagnostic in breast cancer. Moreover, it is a compelling target for therapeutic strategies. Data gathered through this thesis work with the recombinant antibody ScDb-KV11.1/β1 confirms its full potential as a diagnostic and therapeutic tool. More strikingly, the experiments ScDb-KV11.1/β1-TRAIL antibody showed an important and significant effect on all cell lines compared to the simpler ScDb-KV11.1/β1. A lot has been said about organs-on-chips: for example, that they are more realistic models of the human body than are “classic” layers of cells in Petri dishes and could also be more useful than animal models for drug discovery and testing. Of course, these systems might not be able to capture completely the full complexity of organ functions, and struggles could be encountered in recreating aspects of functioning complex signals from, say, the immune and endocrine systems. What stands true, though, is that these systems can undoubtedly recreate a well-mimicked microenvironment, speeding up research, while brining technological advance.