Editorial [Hot Topic: Anti-Cancer Drugs Executive Editor: Elke Bergmann-Leitner]

Intensive research to design chemotherapeutic therapies of cancer has been conducted for the last 70 years. Throughout the decades several groundbreaking observations have been made and countless compounds have been tested for their anti-neoplastic activities. Today we have arrived at a point where we understand in much greater detail the cell biology of tumor cells and are aiming at very specific cellular and nuclear targets. This will lead to much lower toxicities and potentially to wider clinical responses. Moreover, combination therapies combining chemotherapeutic and either radio- or immunotherapy might mark a new milestone in the fight against cancer. The present issue of Anti-Cancer Drugs focuses on novel molecular approaches to cancer treatment and on studies aiding our understanding of the molecular events causing cancer or failure of treatment. As we learn more about the molecular changes in tumor cells and potential escape mechanisms such knowledge will assist in the design of efficacious cancer therapies for a large patient population. S. Bjelogrlic et al. [1] summarize various approaches of molecular targeting to interfere or modulate protein activity or signal transduction in renal cell carcinoma cells. These efforts may lead to reversal of disease mechanism(s). M. Frieden et al. [2] review the novel approach of locked nucleic acids (LNA) for targeting and inhibiting cancer-associated mRNAs. This novel third generation antisense treatment has been shown to be safe and effective and is currently under clinical evaluation. Exploiting deficiencies in tumor cells at the metabolic level are novel anti-cancer strategies reviewed by L. Feun et al. [3]. The authors report on the advances in regards to targeting tumor cells that lack a key enzyme (argininosuccinate synthetase (ASS)). Depriving ASS-deficient cancer cells (e.g., melanoma, hepatocellular carcinoma, renal cancer) of arginine by treatment with an agent such as pegylated arginine deiminase (ADI-PEG) has been shown in Phase I and II clinical trials to exhibit anti-cancer effects. J. Stankova et al. [4] summarize the critical role of folate and methionine metabolism in cancer cells and the targeting in anti-neoplastic therapies. The authors also review their work encompassing the metabolic target methylenetetrahydrofolate reductase and the in vitro and in vivo successes in reducing tumor growth. Similarly, B. Spaenkuch et al. [5] report on the attempt to silence cancer-related genes by antisense oligonucleotides or small interfering RNAs. Such approaches not only target genes that are crucial for the function of tumor cells, but also genes that confer protection by drug-resistance. A different approach to modulating chemoresistance of tumor cells is reviewed by R. Sullivan et al. [6]. The authors assess the adjuvant effect of nitric oxide and nitric oxide mimetic agents for chemotherapy as such treatment frequently restores a chemosensitive phenotype. The mode of action is still under investigation and may be partly caused by increased blood supply, tumor oxygenation, antioxidant effects as well as the downregulation of many cellular enzymes and proteins involved in chemoresistance. Lastly, new strategies revolving around two widely used chemotherapeutic drugs are described: L. Reddy et al. [7] describe new delivery strategies of gemcitabine, a nucleoside analog that will be incorporated by proliferating cells into newly synthesized DNA in place of cytidine and leads to the induction of apoptosis in these cells. T. Liew and L.-X. Yang [8] summarize the efforts of the pharmaceutical field for the design and development of DNA topoisomerase I inhibitors such as camptothecin and its derivatives. I would like to thank all the authors for their efforts in reviewing their own research data and the encompassing body of literature in order to make this issue a comprehensive overview of current efforts to identify and target molecular pathways as well as to discover efficacious novel anti-cancer drugs.....