Editorial [Hot Topic: Enzymes as Useful Tools and Potential Targets in Cancer Chemotherapy (Guest Editor: P. Ruzza and L. Quintieri)]

Cancer is the second leading cause of death in developed societies, and epidemiologists predict that in a few years it will overcome cardiovascular diseases to become the leading cause of mortality. Although the death rate of many forms of cancer seems to decrease, nevertheless most human tumours remain essentially incurable once they have spread, even though the chemotherapy era has been starting over 50 years ago. Luckily, our understanding of the physiology of both normal and neoplastic cells has largely increased in recent years, raising the hope that we can comprehend the molecular abnormalities that distinguish a cancer cell from its normal counterpart. This knowledge will foster the development of targeted molecular approaches that will kill tumour cells while leaving normal tissues untouched, thus increasing the “therapeutic index” of current cytotoxic agents or allowing the design of new specific anticancer drugs. In designing such sophisticated cancer treatments, it is necessary to consider the processes that govern normal cellular physiology. Thus, the goal of this Issue is to explore enzymes of particular importance to human cancer. Studies on enzymes in cancer date back to 1924 when Warburg and co-workers reported that cancer tissues exhibit a greater rate of aerobic glycolysis. Subsequently, many authors have studied tissue enzymes in the attempt to extrapolate theories regarding malignant growth and describing enzymes patterns in neoplastic tissues. Purpose of this Issue is to consider tumour-associated enzymes as targets for chemotherapeutic agents acting as enzyme inhibitors or as enzyme-activated prodrugs. These latter would realize the Ehrlich's concept of a “magic bullet” for the treatment of cancer, being the “magic bullets” compounds with low toxicity to normal tissues and high efficacy against neoplastic cells. This idea, originally associated with antimicrobial agents, unfortunately misses its target with conventional anticancer drugs. While it is impossible to present a fully comprehensive overview in a fast-moving field that encompasses most aspects of cellular physiology, the contributions in this Issue were selected to reflect different and somehow new areas of cancer research, providing a panoramic view of four different classes of enzymes controlling critical cellular events, which are commonly subverted in human cancers. In relation to each of these enzymes, several molecules are discussed regarding organ- or tumor-selective action. In addition, it is concluded that the development of enzyme inhibitors as well as prodrugs has been relatively successful even though all compounds lack a complete selectivity. Therefore, further work is required to explore the differences between normal and cancer cells and to develop optimal enzyme ligands. Undoubtedly, the contributions in this Issue reflect the state-of-the-art in one of the most exciting areas of cancer chemotherapy, but also in cell biology, biochemistry, and molecular genetics. Nonetheless, either enzyme-activated prodrugs or enzyme inhibitors are no longer a topic restricted to sophisticated scientific discussions, since they are already regarded as a leading hope for the future of cancer therapy by clinical oncologists around the world. In this exciting era in which scientific advances and medical practice are rapidly converging, the aim of this volume is to inform and inspire both scientists and physicians toward a common area of interest.