PAR-4 as a possible new target for pancreatic cancer therapy.
BACKGROUND
Pancreatic cancer (PC) is a deadly disease that is intractable to currently available treatment regimens. Although well described in different tumors types, the importance of apoptosis inducer prostate apoptosis response-4 (Par-4) in PC has not been appreciated. PC is an oncogenic kras driven disease, which is known to downregulate Par-4. Therefore, this review highlights its significance and builds a strong case supporting the role of Par-4 as a possible therapeutic target in PC.


METHODS
Literature-based evidence spanning the last 15 years on Par-4 and its significance in PC.


RESULTS
This review provides comprehensive knowledge of the significance of Par-4 and its association with kras status in PC, along with the crosstalk with crucial resistance and survival molecules NF-kappaB and Bcl-2 that ultimately are responsible for the overall poor outcome of different therapeutic approaches in this disease.


CONCLUSIONS
Par-4 holds promise as a potential therapeutic target that can be induced by chemopreventive agents and small-molecule inhibitors either alone or in combination with standard chemotherapeutics leading to selective apoptosis in PC cells. It also acts as a chemosensitizer and therefore warrants further clinical investigations in this disease.
Azmi
Asfar S
AS
Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA. azmia@karmanos.org
Philip
Philip A
PA
Zafar
Syed F
SF
Sarkar
Fazlul H
FH
Mohammad
Ramzi M
RM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C101296:prostate apoptosis response-4 protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins