Editorial [Hot topic: Molecular Mechanisms of Cancer Cell Death (Executive Editor: Ricardo Perez-Tomas)]

The cell death story is still as a current paradigm. Cells may undergo “death” in response to various environmental injuries, or decide to self-destruction in order to ensure proper physiological morphogenesis, preserve tissue homeostasis and eliminate abnormal cells for example in multicellular organisms. Apoptosis and programmed cell death are traditionally used as synonyms and has taken centre stage as the principal mechanism of programmed cell death in mammalian tissues. Programmed cell death should be more accurately defined as cell death that is dependent on genetically encoded signals or activities within the dying cell. In recent years, accumulating evidences suggest that a variety of other molecular cell death pathways have been characterized. Furthermore, the intense focus on apoptosis, and its disturbance in a wide range of human pathologies, perhaps, has blinded us to the significance of these others forms of cell death, and in this special issue “ Molecular mechanisms of cancer cell death” I hope, be useful in putting apoptosis into a broader context. The molecular processes that mediate cell death are more complicated that may have been initially appreciated. Four categories of dynamic cellular activities that lead to cell death have been described: apoptosis, autophagy, necrosis and mitotic catastrophe Permanent growth arrest, known as senescence, is also considered as a type of cell death in the context of cancer therapy [1, 2]. These five cell death class are based on different morphological and biochemical characteristics present in the dying cell. Apoptosis and autophagy have been integrated to be “programmed”, which refers to their strict genetic control. Necrosis and mitotic catastrophe are generally considered passive response to dramatic cellular insult. However, new findings revised in this special issue have demonstrated that these forms of death may also be genetically controlled. Senescence is an essential process of aging and occurs following a gene-direct program involving the erosion of telomeres and the activation of tumor suppression signaling pathway. Acquired defects in signaling pathways that control each of these forms of cell death are among the major hallmarks of cancer. Furthermore, recent evidences suggest that multiple pathways may be activated in single dying cells and cross talk between cell death programs may allow fine control over the ultimate outcome. The inhibition of the dominant molecular route of cell death may not result in survival but, rather, allow the occurrence of alternate programs leading to different types of cell death [3]. Other models of cell death have been described, including caspase-independent apoptosis, necroptosis, paraptosis, pyroptosis, entosis and slow cell death, whose morphologic and biochemical characteristics vary from current definitions of the major cell death pathways describe above [4-6]. In an attempt to simplify this special issue of Current Pharmaceutical Design, only the five best-described cell death outcomes (apoptosis, necrosis, autophagy, mitotic catastrophe and senescence) are presented herein. The whole aim of this special issue is to provide the readers working in basic biomedical sciences and clinicians a comprehensive understanding of different cell deaths involved in human diseases especially neoplastic affections, whose treatment implies the complete understanding of different cell death processes. The first paper by Urriticoechea et al., [7] displayed an overview of recent advances in cancer therapies, focused on to provided the reader to be familiar with the fundamental role of some classic cancer therapies. Following, they focus on the understanding of the value of systemic treatment and on an up-date on the novel, up-coming therapies of the current targeted therapy age, including new antibodies, small molecules, antiangiogenics and viral therapy. The next three papers have dedicated to analyzed deeply the mechanism of apoptosis. Zivny et al. [8] conducted a systematic review of the apoptotic process and its regulation as well as mechanisms of action of conventional anticancer drugs and new promising agents, which trigger directly or indirectly apoptosis of haematological cancer cells. A. Carnero [9] complemented such contribution addressing that the PKB/AKT constitutes an important pathway regulating the signalling of multiple essential biological processes specially those that are able to confer tumorigenic properties in cells. The review's author showed evidences indicating that the AKT pathway is a potential target for cancer chemotherapy. Finally, Hirst and Robson [10] reviewed the role of nitrosative stress as a mediator of apoptosis as well as their implications in cancer treatment.