Pre-clinical and clinical evaluation of apoptosis targeting drugs

• Main Author: Dean, Emma
• Published: University of Manchester 2009
• Subjects: 616.99
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616906

Lung cancer is the leading cause of cancer deaths amongst both men and women and is commonly divided into two histological groups, non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Despite advances in early diagnosis and treatment, chemotherapy provides poor response rates and rare complete remissions, warranting the development of novel therapeutic strategies. Evasion of apoptosis is a hallmark of cancer, allowing malignant cells to survive in hostile micro-environments and to resist chemotherapy with the potential for continued proliferation. This thesis evaluates four novel agents, primarily in lung cancer, in both the pre-clinical and early clinical settings which target key molecules involved in the regulation of apoptosis. Pre-clinical data for XAC 1396-11, a small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), showed induction of apoptotic cell death in a concentration- and time-dependent manner in NSCLC cells.