Cell adhesion-mediated resistance limits the success of
cancer therapies and is a great obstacle to overcome in the clinic. Since the 1990s, where it became clear that adhesion of
tumor cells to the extracellular matrix is an important mediator of
therapy resistance, a lot of work has been conducted to understand the fundamental underlying mechanisms and two paradigms were deduced: cell adhesion-mediated radioresistance (CAM-RR) and cell adhesion-mediated drug resistance (CAM-DR). Preclinical work has evidently demonstrated that targeting of
integrins, adapter
proteins and associated
kinases comprising the cell adhesion resistome is a promising strategy to sensitize
cancer cells to both
radiotherapy and
chemotherapy. Moreover, the cell adhesion resistome fundamentally contributes to adaptation mechanisms induced by
radiochemotherapy as well as molecular drugs to secure a balanced homeostasis of
cancer cells for survival and growth. Intriguingly, this phenomenon provides a basis for synthetic lethal targeted
therapies simultaneously administered to standard
radiochemotherapy. In this review, we summarize current knowledge about the cell adhesion resistome and highlight targeting strategies to override CAM-RR and CAM-DR.