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The form of programmed cell death known as apoptosis has become an intense focus of investigation in various fields including carcinogenesis and cancer therapy. Defects in apoptosis disturb tissue homeostatsis and contribute to the multistep process of carcinogenesis. Since cancer therapy-induced cytotoxicity largely depends on the intact apoptosis signaling cascades, the blockade of apoptotic pathways may enable malignant cells to evade therapy-induced cell death. Treatment failure due to clinical resistance to cancer treatment is common in many types of cancers. With more understanding and accumulation of knowledge in the regulatory and effecter molecules of apoptosis, new strategies and anti-cancer agents have been developed to manipulate the apoptotic balance in cancer cells in favor of apoptosis. In this special issue of Current Cancer Drug Targets (CCDT), five manuscripts summarize recent development in apoptosisrelated carcinogenesis and cancer therapy from different aspects. Cresce and Koropatnick discussed the application of antisense oligonucleotides (ASOs) to arrest tumor growth via targeting Bcl-2 and clusterin. While Bcl-2 is a well-known anti-apoptotic molecule, clusterin is bi-functional, with a nuclear form of clusterin being pro-apoptotic and a secretory form of clusterin being pro-survival . Several protocols of ASOs are currently under clinical trials for several types of cancers, particularly metastatic melanoma and hormone-refractory prostate cancer, both of which are the focus of the discussion in this review. Bcl-2 ASOs have also been used to treat other tumors, for example, lung cancer and ovarian carcinoma, which have been mentioned in the articles by Han and Roman, and Pennington et al. respectively, in this special issue. Han and Roman have systemically described how lung cancer evades apoptotic death followed by analyzing the implications for treatment with various protocols. Pennington et al. nicely summarized how suicide prevention promotes chemoresistance in ovarian carcinoma. Ovarian cancer is one of malignant epithelial cell types. It appears that cross-talk between the tumor microenvironment and malignant epithelial cells may determine apoptotic response. Traditionally, Bid is a typical pro-apoptotic molecule . Recent development has shown that Bid has double roles with respect to stress-response, which is intricately involved in the carcinogenesis and cancer treatment. Song et al. reviewed the recent development in this area, particularly how Bid is activated and how it contributes to the regulation of the cross-talk of cell cycle arrest and apoptosis. Inflammation is associated with the most of, if not all, cancers . Inflammatory molecules frequently affect the apoptotic pathway, and contribute to carcinogenesis and resistance to multiple drug therapy. Among various inflammatory molecules, nuclear factor kappaB (NF-κB), a transcriptional factor, appears to be an important one. Wang and Cho extensively analyzed the role of NF-κB signaling on the apoptotic effect in inflammation-associated carcinogenesis. Increasing evidence has indicated that targeting NF-κB can improve the sensitization of cancer cells to anti-tumor treatment . We believe that this special issue is an essential compilation of up-to-date research on an emerging topic of central concern in the field of apoptosis in carcinogenesis and cancer therapy, which will be useful for anyone interested in this area.
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.