Drug development in pancreatic cancer: finally, biology begets therapy.
Pancreatic cancer is rarely curable, and only 5% of patients achieve long-term survival. The vast majority of patients present with metastatic or unresectable disease. Standard chemotherapy with gemcitabine provides clinical benefit to only a small minority of patients. Thus, the development and investigation of new therapies is clearly needed. As knowledge of the underlying biology of pancreatic cancer has increased, targeted therapies based upon preclinical laboratory work have been developed, and are entering clinical trials. Some of these agents lack traditional dose-limiting toxicities (DLTs) at biologically active doses, and therefore clinical evaluation may not follow traditional guidelines for cytotoxic drug development. This article focuses on targeted therapies currently undergoing clinical evaluation in pancreatic cancer. Classes of therapeutics reviewed include those targeting tumor-microenvironment interactions (matrix metalloproteinase inhibitors, vascular endothelial growth-factor blockade), signal transduction (e.g., farnesyltransferase inhibitors), growth-factor receptors (epidermal growth-factor receptor blockade, Her-2/neu, gastrin), and vaccine approaches. Currently, there is a renewed optimism that the clinical application of biologic understanding will lead to an improved outcome for patients with pancreatic cancer.
Cohen
Steven J
SJ
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Meropol
Neal J
NJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019496:Cancer Vaccines; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018734:Genes, erbB-2; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D004791:Enzyme Inhibitors; D005755:Gastrins; D061965:Matrix Metalloproteinase Inhibitors; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor