Editorial [ Hot topic: Pharmaceutical Design of Novel Anticancer Agents: A Lesson from Nature (Executive Editor: Q. Ping Dou)]

Each year over 6 million people die due to cancer worldwide, which is the second largest single cause of death in both men and women. Fortunately, the war against cancer has been making significant advances in recent years. One of the brightest spots in cancer research has been the discovery of cancer-preventive and anticancer properties in a variety of naturally occurring products which was supported by results from epidemiological, pre-clinical and clinical studies. Although there are limitations for the use of natural products as anti-cancer agents, structure-activity-relationships (SARs) acquired from these products has stimulated researchers to seek out and produce “better” drugs with increased anticancer activity and decreased toxicity. The authors of the first article [1] summarize the current knowledge regarding the anti-cancer effects of two naturally occurring dietary compounds, isoflavone genistein and curcumin, along with their analogs, the SARs, and the regulation of cell signaling by these agents. Both genistein and curcumin exhibit low water solubility, poor in vivo bioavailability and unacceptable pharmacokinetic profiles which limits their efficacy as anti-cancer agents for solid tumors. However, progress has been made in the discovery of synthetic analogs of genistein and curcumin based on their SARs, and of their encapsulation within liposomes or nanoparticles, resulting in enhancement of the anti-tumor activity of these natural agents [1]. The second article focuses on metals, the essential cellular components selected by nature to function in several indispensable biochemical processes for living organisms [2]. Metals are tightly regulated under normal conditions and aberrant metal ion concentrations are associated with various pathological disorders, including cancer. This review article highlights selected metals that have gained considerable interest in both the development and the treatment of cancer. For example, copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However the use of copper-binding ligands to target tumor copper could provide a novel strategy for cancer selective treatment. With known mechanisms of action, novel coordination metal complexes could be designed and evaluated for cancer treatment [2]. Nature also makes many pharmacologically active compounds containing thiazolidine and thiazolidinone scaffolds, which is reviewed in the third article [3]. Based on the preliminary SARs learned from the natural thiazolidine and thiazolidinone compounds, a new generation of analogs containing such unique structures has been designed and synthesized, which subsequently has been demonstrated to possess a broad range of anticancer activities. Therefore taken from nature, the combinatorial library approach has proven to be effective in the discovery and optimization to improve the potency and toxicity of these natural lead compounds. Protein tyrosine phosphatases (PTPs) regulate various cellular activities essential for the initiation and maintenance of malignant phenotypes. The authors of the fourth review article focused on PTPs and their natural and synthetic inhibitors [4]. They discussed the suitability of targeting PTPs for novel anticancer drug discovery and presented several PTPs as examples that have been targeted for anticancer drug discovery. While some PTP inhibitors are currently in use for cancer treatment, development of specific PTP inhibitors as potent anticancer drugs remains in early phase testing. The topical administration of some photoactive natural plant products has been an effective treatment for some skin diseases [5]. The fifth article provides an overview on results achieved to date on state-of-the-art photochemotherapy related to the treatment of human cancer. The authors described the origin and basic principles of photochemotherapy, and provided an overview of two clinically-established phototherapies, Psoralen plus UVA (PUVA) and Photodynamic therapy (PDT), respectively [5]. The last review article describes a natural tumor suppressor protein, Maspin, and its application in human lung cancer. The authors provide evidence that maspin could be a marker that stratifies the progression and prognosis of different subtypes of non small cell lung cancer [6]. Maspin is an epithelial specific member of the serine protease inhibitor (serpin) superfamily but recently identified as an endogenous inhibitor of histone deacetylase 1 (HDAC1). The nature of maspin-mediated HDAC1 inhibition was compared to that of the small molecule HDAC inhibitors. Finally, the authors concluded that nuclear maspin confers better differentiated epithelial phenotypes, decreased tumor angiogenesis, increased tumor sensitivity to drug-induced apoptosis, and a more favorable prognosis [6]....