Molecular biology of pancreatic cancer - Potential clinical implications

The development of cancer involves the accumulation of genetic changes. Ove r the past decade there has a been spectacular advance in the knowledge of the genetic basis of cancer, mainly as a result of the rapid progression of molecular technology. Pancreatic cancer is one of the most lethal cancers. Conventional therapeutic approaches have not had much impact on the course of this aggressive neoplasm. Knowledge of the molecular biology of pancrea tic cancer has grown rapidly. Genetic alterations in pancreatic cancer incl ude oncogene mutations (most commonly K-ras mutations), and tumour suppress or gene alterations (mainly p53, p16, DCC, etc.). These advances have poten tial implications for the management of this deadly disease. Identification of a hereditary genetic predisposition to pancreatic cancer has led to the formation of pancreatic cancer registries around the world, with voluntary screening of patients and siblings for the hereditary genetic defect. Asym ptomatic population screening remains unrealistic, but the recognition of s ubpopulations at increased risk from pancreatic cancer, along with novel an d sensitive detection techniques, means that targeted population screening is a step closer. Intensive research is performed in specialist laboratorie s to improve the diagnostic approach in patients with pancreatic cancer. Th e use of such molecular diagnostic methods is likely to expand. Molecular b iology may also have a great impact on the treatment of pancreatic cancer, and many therapeutic approaches are being evaluated in clinical trials, inc luding gene replacement therapy, genetic prodrug activation therapy, antise nse immunology and peptide technology. The 'molecular age' has the promise of delivering still better results. This review summarises recent data rela ting to the molecular biology of pancreatic cancer, with emphasis on featur es that may be of clinical significance for diagnosis and/or therapy.