Current Medicinal Chemistry - Anti-Cancer Agents - Volume 3, Issue 4, 2003

Anticancer agents are used to kill tumour cells with collateral damage as limited as possible. One of the cell death triggered by these agents is apoptosis, an orderly and synchronised process that involves a mitochondrial-dependent, Bcl-2 regulated pathway ending with caspase activation. In this issue of Current Medical Chemistry - Anticancer Agents, five different aspects of tumour cell apoptosis triggered by chemotherap Read More

Apoptosis, the cell's intrinsic death program, is a key regulator of tissue homeostasis. An imbalance between cell death and proliferation may result in tumor formation. Also, killing of cancer cells by cytotoxic therapies, such as chemotherapy, γ-irradiation or ligation of death receptors is predominantly mediated by triggering apoptosis in target cells. Death receptor signaling pathways have been implied to contribute to th Read More

DNA damaging agents such as 1-β-D-arabinofuranosylcytosine (Ara-C) and daunorubicin (DNR) are widely used in the treatment of acute nonlymphocytic leukemia. These drugs have, of course, been the objects of intense basic research, as well as preclinical and clinical study. Although specific biochemical lesions (DNA damage) have been associated with Ara-C- and DNR-mediated cytotoxicity, the pathways leading to th Read More

Topoisomerase inhibitors are among the most efficient inducers of apoptosis. The main pathways leading from topoisomerase-mediated DNA damage to cell death involve activation of caspases in the cytoplasm by proapoptotic molecules released from mitochondria. In some cells, apoptotic response also involves the death receptor Fas (APO-1 / CD95). The engagement of these apoptotic effector pathways is tightly Read More

Docetaxel (Taxotere) is a member of the taxane class of anticancer agents to reach clinical use. This semisynthetic analog of paclitaxel (Taxol) is one of the newer potent anti-neoplastic agents now undergoing extensive laboratory and clinical investigations. Several studies indicate that antimicrotubule agents are potent promoters of apoptosis in cancer cells. Cytotoxic mechanisms of antimitotic taxoids are not yet fully u Read More

Proteins of the Bcl-2 family share one or several Bcl-2 homology (BH) regions and behave as pro- or antiapoptotic proteins. Prosurvival members such as Bcl-2 and Bcl-XL are supposed to preserve mitochondrial outer membrane integrity, thus preventing the release of soluble apoptogenic molecules. Pro-apoptotic members include BH3- only proteins that act as sensors of cellular damage and initiate the death process and Read More