Claspin and Cancer: Where Are We Now?

Cancer cells arise from the cumulative acquisition of genetic and epigenetic alterations that affect vital cellular functions. Genomic instability results from deficiencies in protective mechanisms, such as cell cycle checkpoints, DNA replication control, or DNA repair. Claspin integrates a group of crucial proteins that maintain genome integrity. It participates in key cellular events such as DNA damage checkpoint activation, DNA replication, replication stress responses, DNA repair, epigenetic memory, and apoptosis. Given its crucial functions, a role for Claspin in cancer is not a surprise. Indeed, there is a considerable body of evidence linking Claspin deregulation with cancer. For instance, over-expression of Claspin and Tim promoted the survival of cancer cells by enabling adaptation to oncogene-induced replication stress. In addition, Claspin gene (CLSPN) mutations that affect checkpoint regulation have been identified in cancer patients, suggesting that they may contribute to cancer development. Changes in Claspin expression levels may be used as a prognostic marker in several types of cancer. Finally, several therapy-resistance signaling pathways seem to converge onto Claspin's stabilization, turning Claspin into an attractive target for chemo- and radio-sensitization. In this review, we will focus on the role of Claspin in cancer and ways in which Claspin can be exploited in cancer therapy.