the role of epigenetics in resistance to cisplatin chemotherapy in lung cancer表观遗传学在抵抗顺铂化疗的肺癌.pdfVIP

Cancers 2011, 3, 1426-1453; doi:10.3390/cancers3011426 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review The Role of Epigenetics in Resistance to Cisplatin Chemotherapy in Lung Cancer Kenneth J. O’Byrne, Martin P. Barr and Steven G. Gray * Trinity College Dublin, Department of Clinical Medicine, Trinity Centre for Health Sciences, St James Hospital, James Street, Dublin 8, Ireland; E-Mails: kobyrne@stjames.ie (K.J.O.); mbarr@stjames.ie (M.P.B.) * Author to whom correspondence should be addressed; E-Mail: sgray@stjames.ie; Tel.: +353-1-896-3620. Received: 29 December 2010; in revised form: 9 March 2011 / Accepted: 10 March 2011 / Published: 17 March 2011 Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. Keywords: epigenetics; histone; post-translational modification; DNA methylation; epigenetic modifiers; cisplatin; NSCLC 1. Introduction Lung cancer is the cancer with the highest mortality a