Molecular targeting therapy for pancreatic cancer.
Pancreatic carcinogenesis is driven by multiple genetic and epigenetic changes. The epidermal growth factor receptor (EGFR) and its downstream signaling pathways, Ras-Raf-MEK-ERK axis, play important roles in pancreatic cancer development. The phosphoinositol 3 kinase (PI3 K)/Akt and the nuclear factor kappaB (NF-kappaB) pathways control both proliferation and resistance to apoptosis of pancreatic cancer. The role of cyclooxygenase (COX) and lipoxygenase (LOX) in the development of pancreatic cancer has been made known recently. The elucidation of these molecular events has led to several distinct therapeutic advances, including therapies that target EGFR, the Ras-Raf-MEK-ERK axis, the COX-2 and LOX pathways, and others. Many novel agents have been developed and are undergoing clinical investigation, such as monoclonal antibodies against EGFR, tyrosine kinase inhibitors (TKIs), farnesyl transferase inhibitors (FTIs), Bay43-9006, CI-1040, CCI-779, celecoxib, and LY293111. This review highlights recent advances in the development of these agents.
Xiong
Henry Q
HQ
Department of Gastrointestinal Medical Oncology, Unit 426, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. qxiong@mdanderson.org
D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; C496540:PTGS2 protein, human