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

Topoisomerase II is the target of several anticancer agents. The discovery of a second enzyme, called topoisomerase II β, genetically distinct from a, prompted the investigation on the different functional roles of the two isoforms. Whereas the first recognized isozyme is essential for life due to its role in chromosome condensation and segregation, beta functions remained elusive, although its importance in neural development i Read More

The potential anticancer activities of histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors have been extensively studied in recent years. HDAC inhibitors suppress the activities of multiple HDACs, leading to an increase in histone acetylation. This histone acetylation induces an enhancement of the expression of specific genes that elicit extensive cellular morphologic and metabolic change Read More

Signal transduction pathways are frequently altered in human breast cancer and are the targets of several novel therapies currently in clinical trials. Therapeutic strategies include extracellular blockade of tyrosine kinase receptors with the monoclonal antibodies C225 and trastuzumab. Competitive inhibitors of adenosine triphosphate binding sites on tyrosine and serine / threonine kinases are also being evaluated in pha Read More

Selective aberrant cell suicide (ie., apoptosis or programmed cell death) is a hallmark of “nonneoplastic” tissue. In cells that have clonally evolved or in common parlance “cancer cells”, apoptosis is either itself aberrant or completely inhibited. Strategies to enhance apoptosis under conditions of cancer cellular stress is an evolving and actively investigated area of experimental therapeutics. Bcl2 proteins are key mediators of th Read More

Pharmacogenetics focuses on intersubjects variation in therapeutic drug effects and toxicity depending on genetic polymorphisms. This is particularly interesting in oncology since anticancer drugs usually have a narrow margin of safety. Irinotecan {7-ethyl-10-[4-(1- piperidino)-1-piperidino]carbonyloxycamptothecin} is used in cancer chemotherapy as a topoisomerase I inhibitor and it is characterised by a someti Read More

The Peroxisome Proliferator Activated Receptors (PPARs) are initially described as molecular targets for compounds inducing peroxisome proliferation. Among the three PPAR subtypes (alpha, beta, gamma), PPAR-gamma acting as a ligand-activated transcription factor, proved to be an important regulator of adipogenic differentiation and glucose homeostasis. Recent data support evidence for participation of PPAR-gam Read More