TY - JOUR
T1 - Poly(ADP-Ribose) polymerases new players in the pathogenesis of exocrine pancreatic diseases
AU - Martínez-Bosch, Neus
AU - Fernández-Zapico, Martin E.
AU - Navarro, Pilar
AU - Yélamos, José
N1 - Publisher Copyright:
© 2016 American Society for Investigative Pathology.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - The poly(ADP-ribose) polymerase (PARP) enzymes were initially characterized as sensors of DNA breaks but are now known to play key roles not only in the DNA damage response but also in regulating numerous molecular processes, such as gene transcription. Furthermore, these polymerases have emerged as key players in the pathogenesis of multiple diseases, providing promising therapeutic targets for pathologies such as cardiovascular disorders, neurodegenerative diseases, and cancer. In recent years, PARPs have been implicated in the pathogenesis of pancreatitis and pancreatic cancer, and PARP inhibition has been proposed as a valuable strategy for treating these two important gastrointestinal tract disorders. For instance, in preclinical mouse models, pancreatitis was significantly attenuated after genetic or pharmacological PARP inactivation, and several clinical trials have demonstrated promising responses to PARP inhibitors in pancreatic cancer patients. In this review, we summarize the current understanding of PARP functions in these two dismal pathologies and discuss the next steps necessary to determine whether PARP inhibitors will finally make the difference in treating pancreatitis and pancreatic cancer successfully.
AB - The poly(ADP-ribose) polymerase (PARP) enzymes were initially characterized as sensors of DNA breaks but are now known to play key roles not only in the DNA damage response but also in regulating numerous molecular processes, such as gene transcription. Furthermore, these polymerases have emerged as key players in the pathogenesis of multiple diseases, providing promising therapeutic targets for pathologies such as cardiovascular disorders, neurodegenerative diseases, and cancer. In recent years, PARPs have been implicated in the pathogenesis of pancreatitis and pancreatic cancer, and PARP inhibition has been proposed as a valuable strategy for treating these two important gastrointestinal tract disorders. For instance, in preclinical mouse models, pancreatitis was significantly attenuated after genetic or pharmacological PARP inactivation, and several clinical trials have demonstrated promising responses to PARP inhibitors in pancreatic cancer patients. In this review, we summarize the current understanding of PARP functions in these two dismal pathologies and discuss the next steps necessary to determine whether PARP inhibitors will finally make the difference in treating pancreatitis and pancreatic cancer successfully.
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U2 - 10.1016/j.ajpath.2015.09.021
DO - 10.1016/j.ajpath.2015.09.021
M3 - Review article
C2 - 26687988
AN - SCOPUS:84955308982
SN - 0002-9440
VL - 186
SP - 234
EP - 241
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -