Preface [Hot Topic: Cellular Targets for Anti-Cancer Therapy (Guest Editor: Alexander A. Shtil)]

This issue of CURRENT DRUG TARGETS is focused on cancer therapy, one of the most challenging problems for humanity. Indeed, this problem represents the nexus of life science with many other disciplines. Outburst of modern biology uncovers the fundamental mechanisms of single cell behavior (e.g., gene expression regulation, macromolecular biosynthesis and transport, cell cycle progression, division, death) which, in turn, sets stage for understanding tumor cell-organism interactions such as control of differentiation, clonal proliferation, evasion from surveillance, to mention a few major paradigms of cancer biology. This basic knowledge needs to be translated into therapeutically applicable strategies, a task for unified efforts of biologists and medical doctors with pharmacologists, physico-chemists, medicinal chemists... The contributors to the present volume, although their areas of expertise differ, follow the key principle of mechanism based anticancer therapy, namely, identification of a particular structure critical for cancer cell and search for means of targeting the process(-es) in which this structure is involved. For the deliberate therapeutic intervention the authors analyze signal transduction machinery, drug metabolism systems, and cell death cascades. The importance of preferential accumulation of the killer in the tumor over normal tissues is emphasized in novel approaches for delivery of small molecules and genetic constructs. We sought to combine laboratory investigations with clinically relevant topics; a trend for 'translational approach' is demonstrated in the studies of individual mechanisms as predictive factors of response to therapy. Still the major question remains to be resolved: would the intervention into one single mechanism be sufficient for successful treatment? It is the redundant regulation of key cellular functions, the notorious biological plasticity that allows tumor cells to escape treatment. If cancer is the 'unfolding' of this plasticity, the 'grown-to-perfection' ability to avoid control, then little is left for a simplified hope. This by no means underscores the necessity for studying cancer related mechanisms: rather, these investigations build the foundation for manipulation with multiple targets. The more processes in tumor cells become available for therapeutic management the better should be the outcome. One should believe that enormous intellectual effort and unprecedented material investment aimed at cancer treatment will be justified by any advancement in this everlasting enigma, as complex as life itself...