Calpains as potential anti-cancer targets

Introduction: The intracellular signaling cysteine proteases, calpains (specifically the ubiquitous calpains 1 and 2), are involved in numerous physiological and pathological phenomena. Several works have highlighted the implication of calpains in processes crucial for cancer development and progression. For these reasons, calpains are considered by several authors as potential anti-cancer targets. Areas covered: How calpains are implicated in cancer formation and development, how these enzymes are deregulated in cancer cells and how these proteases could be targeted by anti-cancer drugs. Studies published in the last 10 years are focused on. Expert opinion: Targeting calpain activity with specific inhibitors could be a novel approach to limiting development of primary tumors and formation of metastases, by inhibiting tumor cell migration and invasion, which allows dissemination as well as tumor neovascularization, which in turn allows expansion. However, such drugs could interfere with anti-cancer treatments, as ubiquitous calpains play crucial roles in chemotherapy-induced apoptosis. For these reasons, drugs targeting calpains would have to be used selectively to avoid interference with other treatments and physiological processes. Further studies will be required concerning the other members of the calpain family and their potential implication in cancer development before considering treatments targeting their activity.