Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP. | Yuan et al. Journal of Hematology Oncology 2011 4 16 http content 4 1 16 JOURNAL OF HEMATOLOGY ONCOLOGY REVIEW Open Access Novel targeted therapeutics inhibitors of MDM2 ALK and PARP Yuan Yuan1 Yu-Min Liao2 Chung-Tsen Hsueh1 and Hamid R Mirshahidi1 Abstract We reviewed preclinical data and clinical development of MDM2 murine double minute 2 ALK anaplastic lymphoma kinase and PARP poly ADP-ribose polymerase inhibitors. MDM2 binds to p53 and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13 of non-small cell lung cancer NSCLC . Early-phase clinical studies with Crizotinib an ALK inhibitor in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib another oral small-molecule PARP inhibitor demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation. Introduction Modern cancer therapeutics has evolved from non-specific cytotoxic agents that affect both normal and cancer cells to targeted therapies and personalized medicine. Targeted therapies are directed at unique molecular signature of cancer cells to produce greater efficacy with less toxicity. The development and use of such therapeutics allow us to practice personalized medicine and improve cancer care. In this review we summarized pre-clinical data and .
