Current Cancer Drug Targets - Volume 8, Issue 2, 2008

The evolutionarily conserved process of apoptosis plays an important role in removing cells during development and in maintaining tissue homeostasis. However, dysregulation of apoptosis, leading to too much or too little cell death, contributes to a number of diseases including cancer. Designing anti-cancer therapeutic solutions requires the understanding of the interplay between positive and negative regulators of the Read More

Approximately 50% of sporadic human tumors harbor somatic mutations in the p53 gene locus, while germ line mutations confer a high familial risk and are associated with Li-Fraumeni Syndrome patients. The p53 tumor suppressor protein is often referred to as the “guardian of the genome” since its response to DNA-damage or checkpoint failure gives rise to a series of anti-proliferative responses. One of the most i Read More

Cytotoxic approaches to killing tumor cells, such as chemotherapeutic agents, γ-irradiation, suicide genes or immunotherapy, have been shown to induce cell death through apoptosis. The intrinsic apoptotic pathway is activated following treatment with cytotoxic drugs, and these reactions ultimately lead to the activation of caspases, which promote cell death in tumor cells. In addition, activation of the extrinsic apoptotic pa Read More

Apoptosis, or programmed cell death, is a cell suicide process with a major role in development and homeostasis in vertebrates and invertebrates. Dysregulation of apoptosis leading to early cell death or the absence of normal cell death contributes to a number of disease conditions including neurodegenerative diseases and cancer. Inhibition of apoptosis enhances the survival of cancer cells and facilitates their escape from i Read More

Ubiquitylation is an essential cellular process, and yet many cancer cells appear to be more reliant upon it than normal cells as they are surprisingly sensitive to proteasome inhibitors (PI) and proteasome inhibitor drugs are well tolerated in vivo. Several reviews have suggested that specific protein targets account for PI induced cell death, but fail to adequately explain why cancer cells are more sensitive than normal cells to Read More

Since the discovery of tumor necrosis factor (TNF)-alpha, researchers have pursued many approaches to harness the potency of TNF-alpha and TNF superfamily members to treat human cancers. Several ligands of the TNF superfamily, including TNF-alpha, lymphotoxin, FAS ligand (FasL), and APO2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) have been tested in various stages of clinical research for their anti-tu Read More

Triggering apoptosis, the cell's intrinsic death program, is a promising approach for cancer therapy. TNF-related apoptosisinducing ligand (TRAIL), a member of the TNF superfamily of death inducing ligands, is of special interest for cancer therapy, since TRAIL has been shown to predominantly kill cancer cells, while sparing normal cells. However, since many cancers fail to undergo apoptosis in response to TRAIL treatment, TRAI Read More

In Europe more than 3 million individuals develop a malignancy annually. Despite recent progress in screening, diagnosis and therapy of most cancers, prognosis remains poor and only a minority of patients are cured. This owes to the fact that most cancers are diagnosed in advanced stages and due to the fact that treatment options for most cancers are limited. While there has been a substantial improvement in syste Read More

Prostate cancer is the most common cancer in men and one of the leading causes of cancer-related deaths in Western countries. The extraordinary biological heterogeneity, the increasing incidence of this disease, and the presence of putative premalignant conditions make prostate cancer a crucial pathology to study and test pharmacological or nutritional chemopreventive strategies. It has been demonstra Read More

For many years, alkylating agents and purine nucleoside analogs (PNA) have been considered the drug of choice for treatment of chronic lymphocytic leukemia (CLL). More recently the introduction of monoclonal antibodies (mAb), especially rituximab directed against CD20 and alemtuzumab directed against CD52, has renewed interest in CLL therapy. Over the last few years, several new mAbs directed against ly Read More