Editorial [Hot Topic:Preamble: CDC25 Phosphatases in Cancer and CDC25 Inhibitors (Guest Editor: Gregoire Pierre Prevost)]

The fight against cancer progresses regularly with continuous efforts on prevention, diagnostic, surgery, chemo- and radiotherapy. Nevertheless, the cancer disease still remains a leading life-threatening pathology in a large number of indications. In that sense, there is still a huge need for novel therapeutic strategies. Based on the increasing knowledge of the biology of the cancer(s), novel original strategies to treat cancer patients emerge day after day. In this special issue, we are covering one of these new targets: CDC25 phosphatase, with all the latest and outstanding developments in research supporting that CDC25 phosphatase would be a novel therapeutic target against cancer. Briefly, the name CDC25 is coming from Cell division cycle 25 (CDC25) and is represented by three family members in the human genome: CDC25A, CDC25B and CDC25C which are all key actors in eukaryotic cell cycle control. They are responsible for the dephosphorylations that activate the cyclin-dependent kinases (CDK) at specific stages of the cell cycle and also central regulators of the G2/M checkpoint mechanisms activated in response to DNA injury. The expression and activity of these enzymes are finely regulated by multiple mechanisms including post-translational modifications, interactions with regulatory partners, control of their intracellular localization, and cell cycleregulated degradation (see review Bernadette Aressy and Bernard Ducommun). The specific role for each of these three proteins is still under investigation showing both different and redundant specificities and regulations not shared by all the members (see review Anne Fernandez- Vidal, Anne Mazars, & Stephane Manenti). Altered expression of these phosphatases is associated with checkpoint bypass and genetic instability. Accordingly, increased expressions of CDC25 (A, B & C) are found in many high-grade tumors and are frequently correlated with poor prognosis in human cancers. Studies using mouse models demonstrated that deregulated expression of CDC25A significantly promotes RAS- or NEU-induced mammary tumor development with chromosomal aberrations, whereas decreased CDC25A expression in heterozygous knockout mice delays tumorigenesis. These biological properties of CDC25 phosphatases provide significant insight into the pathobiology of cancer and scientific foundation for anti-CDC25 therapeutic intervention (see review: Hiroaki Kiyokawa and Dipankar Ray). These protein tyrosine phosphatases are therefore recognized as attractive molecular targets for small molecules. Consequently, challenges for developing small molecule inhibitors of the Cdc25 family and a number of potential chemical probes are discussed and their characteristics are summarized (see review: John S. Lazo and Peter Wipf; M-C. Brezak et al.; A. Lavecchia et al.). Finally, one key example of preclinical studies using a CDC25 inhibitor has been presented by the group of B. Carr (see review: Ziqiu Wang, Siddhartha Kar & Brian I. Carr) which may provide new means to control cancers of the liver and other sites. All the papers associated in this book describe an increasing body of evidence on the role of CDC25 in cancer progression. All these reviews cover complementary aspects of CDC25: the role of CDC25s in the normal cell and during the tumorigenesis, the consideration of CDC25 as a relevant druggable target, the discovery of new cdc25 inhibitors and finally the preclinical approaches. Such a special issue will allow every one who wishes to be informed and updated with the latest and most important developments in the CDC25 field.