Cell-cycle dysregulation and anticancer therapy.

Trends Pharmacol Sci

Department of Biochemistry, Center in Molecular Toxicology and the Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Published: March 2003

Cell-cycle dysregulation is a hallmark of tumor cells. The ability of normal cells to undergo cell-cycle arrest after damage to DNA is crucial for the maintenance of genomic integrity. The biochemical pathways that stop the cell cycle in response to cellular stressors are called checkpoints. Defective checkpoint function results in genetic modifications that contribute to tumorigenesis. The regulation of checkpoint signaling also has important clinical implications because the abrogation of checkpoint function can alter the sensitivity of tumor cells to chemotherapeutics. Here, we provide an overview of the mechanisms that regulate the cell cycle, current anticancer therapies that target checkpoint signaling pathways, and strategies for the development of novel chemotherapeutic agents.

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http://dx.doi.org/10.1016/S0165-6147(03)00026-9DOI Listing

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