Cancer therapy: targeting cell cycle regulators.
Cyclins and CDKs play critical roles in DNA synthesis and cell division. Alterations in their function may lead to the disruption of normal cell growth and apoptosis, and subsequently, result in carcinogenesis. Elevated levels of cyclins and CDKs are frequently observed in a wide range of different types of human cancers. Understanding of molecular mechanisms underlying the cell cycle effects in response to the chemotherapeutic agents is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to chemotherapeutic agents. Despite the clinical applications of cell cycle specific chemotherapeutic agents, there is still an urgent need to develop novel drugs that can target multiple sites and pathways of the cell cycle while avoiding drug induced cytotoxicity. In this review article, we will summarize the development of novel agents that specifically target cell cycle pathways in human cancer. We will discuss drugs that can directly interfere with the mitotic process of tumor cells. Moreover, we tend to address the significance of using small molecule CDK inhibitors that are derived from natural products.
Department of Laboratory Medicine, Lund University, Malmö University Hospital, 205 02, Malmö, Sweden.
Martin
M
Johansson
Jenny Liao
JL
Persson
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D016213:Cyclins; D018844:Cyclin-Dependent Kinases