Current Pharmaceutical Design - Volume 16, Issue 1, 2010

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 pri Read More

The landscape of cancer treatment has dramatically changed over the last four decades. The age when surgery and radiotherapy were the only effective way to fight tumour growth has ended. A complex scenario where the molecular features of tumours seem to be the cornerstone of any therapy is now emerging. Here we provide an overview on the different approaches to cancer treatment. This review will help the reade Read More

Apoptosis is a normal aspect of human physiology ensuring tissue homeostasis. Evasion of endogenous cell death processes, including apoptosis, represents one of the characteristics of cancer. Defects in the physiological mechanisms of apoptosis contribute to the pathological cell expansion and to the development and progression of cancer. Resistance of malignant cells to cancer therapeutic agents may be, in some cases, c Read More

PKB/AKT constitutes an important pathway that regulates the signaling of multiple essential biological processes. PTEN is a dual protein/lipid phosphatase whose main substrate is phosphatidyl-inositol,3,4,5 triphosphate (PIP3), the product of PI3K. Increases in PIP3 result in the recruitment of PDK1 and AKT to the membrane where they are activated. Furthermore, PI3K can be activated by direct binding to oncogenic Ras pr Read More

Nitric oxide (NO°) is now recognised as one of the most important molecules influencing the development, progression and treatment of cancer. A key component of its action is as a negative and positive regulator of apoptosis. Broadly, constitutive levels of NO° (nM), are capable of inhibiting numerous signalling pathways in both normal and cancer cells. These include soluble guanylate cyclase, leading to reduced Ca++ signal Read More

Until recently, necrosis, unlike apoptosis, was considered as passive and unregulated form of cell death. However, during the last decade a number of experimental data demonstrated that, except under extreme conditions, necrosis may be a well-regulated process activated by rather specific physiological and pathological stimuli. In this review, we consider mechanisms and the role of necrosis in tumor cells. It became recently Read More

Mitotic catastrophe is a mechanism of cell death characterized by the occurrence of aberrant mitosis with the formation of large cells that contain multiple nuclei, which are morphologically distinguishable from apoptotic cells. Sometimes, mitotic catastrophe is used restrictively to indicate a type of cell death that occurs during or after a faulty mitosis leading to cell death, which takes place via necrosis or apoptosis, rather tha Read More

Senescence is defined as an irreversible growth arrest that is characterised by a changed morphology, gene expression pattern and chromatin structure as well as an activated DNA damage response. Senescence has a dual role for tumour development. Firstly, it acts as a tumour suppressor to prevent the proliferation of seriously damaged cells. Important mechanisms ensuring the stop of genomically altered cells Read More

Autophagy is an evolutionarily conserved degradation pathway which primary functions as a cell survival adaptive mechanism during stress conditions. Autophagy is a tumor suppressor process and induction of the autophagic machinery can cause cell demise in apoptosis-resistant cancer. Thus, this metabolic pathway can act either to prevent or to promote carcinogenesis, as well as to modulate the response to ant Read More

Aberrantly regulated apoptosis is involved in the pathogenesis of several diseases and defective apoptosis leads to uncontrolled cell proliferation and tumorigenesis. Cancer is an example of a pathologic condition where the normal mechanisms of cell cycle regulation are dysfunctional either by excessive cell proliferation, inhibited/suppressed apoptosis or both. Dietary habits are estimated to contribute to, at least, one third of Read More