New aspects of regulatory signaling pathways and novel therapies in pancreatic cancer.
Pancreatic cancer is an exceptionally devastating and incurable disease, the treatment of which has largely been unsuccessful due to higher resistance of pancreatic tumor cells to conventional approaches including surgery, radiation and/or chemotherapy. Therefore, there is a need for development of new and effective chemotherapeutic agents which can target multiple signaling pathways to induce responsiveness of pancreatic cancer cells to death signals. Although crucial advances in our understanding of the molecular pathogenesis of the disease have been made, the exceptional aggressiveness of pancreatic cancer remains largely unexplained. Investigators have actively investigated to elucidate molecular mechanisms involved in the oncogenesis, growth, invasion and metastasis of this malignancy. Pancreatic tumor cells have developed remarkable defense mechanisms to evade apoptosis and to increase their resistance to several drugs. All the typical signs of apoptosis are the final results of a complex biochemical cascade of events, whose proper function is regulated by growth and transcriptional factors, hormones and other molecules affecting the intracellular signal transduction. Understanding these complex mechanisms has created new hopes concerning pancreatic cancer in the last years and has evoked new therapeutic approaches, many of which undergo clinical trials with promising results to date. The present review provides a comprehensive description of the molecular signaling mainly of the apoptotic pathways implicated in the pathogenesis of pancreatic cancer, an incentive on the potential pathogenetic role of Helicobacter pylori infection and an appraisal of the most recent therapeutic strategies aiming at the repair of molecular lesions and applied at a cell biochemical level.
Diamantidis
Michael
M
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
Tsapournas
Georgios
G
Kountouras
Jannis
J
Zavos
Christos
C
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D051242:Caveolin 1 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D054353:Perforin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D000077584:2-Methoxyestradiol; D051017:Apoptosis Regulatory Proteins; D051242:Caveolin 1; D016213:Cyclins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004958:Estradiol; D053222:Fas Ligand Protein; D053804:Granzymes; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D020928:Mitogen-Activated Protein Kinases; D009077:Mucins; D009479:Neuropeptides; D054353:Perforin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051880:Receptors, Notch; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C495540:CAV1 protein, human; C412403:DIABLO protein, human; C505653:TNFSF10 protein, human; C496540:PTGS2 protein, human