oa Editorial [Hot topic: Role of Apoptosis in Chemotherapy (Guest Editors: George G. Chen and Paul B.S. Lai)]

The term of apoptosis was introduced in 1972 by Kerr et al. to describe a genetically programmed cellular process of cell dearth [1], which forms an integral part of the life cycle of higher organism. Nearly 40 years later, apoptosis has been regarded as a primary cause or a secondary effect in various diseases including cancers, and has appeared to be a very productive “factory” for the development of new therapeutics. Chemotherapy is the mainstay of cancer treatment. Most, if not all, chemotherapeutic agents kill cancer cells by targeting one or more key apoptotic molecules. However, cancer cells frequently develop different mechanisms to evade apoptosis, making them insensitive to chemotherapeutic agents [2,3]. In order to overcome the chemoresistance, we have to understand how apoptotic pathways are executed in cancer cells, and to generate novel chemotherapeutic agents/protocols that can significantly and specifically induce apoptosis in cancer cells. There are a burgeoning number of studies on the development of new anti-tumor agents that target apoptotic molecules. However, articles that systemically summarize these new developments somehow do not get timely update. According to the available information from Pubmed, the most recent review papers on apoptosis and chemotherapy were published around 3-4 years ago. In this special issue of Current Drug Targets, entitled “apoptosis and chemotherapy”, seven review articles are focused on different aspects of chemotherapy and apoptosis. Ahmad et al. excellently review the modulatory effects of cruciferous vegetable-derived indole compounds, particularly indole-3-carbinol and its dimeric product, 3, 3' diindolylmethane, on apoptotic-related molecules such as survivin, uPA/uPAR and NF-κB. The convincing evidence supports that the chemosensitizing properties of these indole compounds are achieved by inducing apoptosis. In addition to vegetables, potential chemotherapeutic agents have also been discovered in a variety of other sources. The development of the marine organismderived apoptosis-inducing compounds that possess chemotherapeutic property is still in its neonatal age. The article by Lin et al. evidently shows the great potential in this novel area by reviewing apoptosis-inducing and anticancer activities of several compounds isolated from marine organisms. Yang and Dou nicely summarize molecular targets and biological properties of terpenoids that are a group of natural compounds found in a variety of fruits, vegetables and medicinal plants. Some of the terpenoids are able to induce tumor cell death by inhibiting multiple cancer-specific targets including the proteasome, NF-κB, and Bcl-2. Due to the fact that some of the terpenoids are structurally similar to human hormones, these terpenoids appear to be particularly applicable for hormone-related tumors such as breast and prostate cancers. Article by Chung and Irwin provides valuable insights into how targeting multiple members of the family of p53 proteins including p53, p63, and p73 can greatly enhance the inhibition of cancer cell growth. The regulatory pathways controlling the p53-family proteins contribute to the apoptosis in a variety of cancer cells. Understanding these regulatory pathways will indubitably benefit the development of novel chemotherapeutic agents. There is a close relationship between gastro-intestinal cancers and epithelial growth factor receptor (EGFR). Kanwar et al. discuss different approaches to change the level of EGFR in gastrointestinal malignancies. These approaches include antibodies, small molecule EGFR tyrosine kinase inhibitors, gene mutations and dietary agents, through which the chemotherapy of gastro-intestinal cancers will be significantly affected. Karnak and Xu analyze the various approaches to modulate Bcl-2 family proteins in prostate cancer. Overexpression of the anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 are often associated with prostate cancer and contribute to chemoresistance. Therapeutic strategies including DNA anti-sense, RNA interference, small molecule inhibitors and peptides have been designed to either limit the source or disrupt the interactions of these pro-survival Bcl-2 family members, therefore resuming or improving the sensitivity of the cancer cells to chemotherapy. Liu et al. systemically describe the recent advances in chemotherapies for thyroid cancer. These treatments target various molecules in the key steps of thyroid carcinogenesis by either enhancing pro-apoptotic molecules or suppressing anti-apoptotic ones. Much of the attention is devoted to the compounds targeting thyroid cancer cells that do not normally respond to traditional therapy. We sincerely hope that this special issue is an important source of information that is useful for anyone interested in the role of apoptosis in chemotherapy and that stimulates the development of novel treatments for cancers.