Mechanisms and Drug Targets for Pancreatic Cancer Chemoprevention.
BACKGROUND
Pancreatic cancer management remains a major challenge to society. Poor prognosis results in dismal patient survival rates and quality of life post chemo/radiation therapies. Although progress has been made in drug development for targeting pancreatic cancer, accompanying issues of drug resistance renders it futile. While intake of fruits and vegetables in routine diets has been linked to reduced risk of pancreatic cancer, a wide variety of natural agents are being evaluated as adjuvant therapies in combination with frontline chemotherapeutics in pancreatic cancer clinical trials.


OBJECTIVE
This review highlights the emerging area of cancer chemoprevention with natural/ dietary compounds serving as novel agents possessing strong anticancer properties; these are pleiotropic agents targeting multiple pathways with minimal toxicity in normal tissue.


METHODS
We employed extensive literature search and considered all the relevant information presented in a concise, well-balanced and structured format.


RESULTS
Completed and ongoing human studies with natural agents have shown surprisingly successful rates for regulating pancreatic carcinogenesis. Combinatorial therapies with synthetic, approved drugs and natural agents not only improved the patient response rates, but also helped in overcoming drug resistance and inducing chemosensitivity to the resistant tumors, as opposed to monotherapies for pancreatic cancer chemoprevention.


CONCLUSIONS
The current review focuses on the available chemotherapeutic drugs and their limitations, and moves on to discuss the wide realm of chemopreventive efficacy that the natural agents have to offer. It discusses the underlying mechanisms of action and available information, from extensive literature analysis, to highlight the novelty of these agents for their antitumor effects against pancreatic cancer.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.
Deepanshi
D
Dhar
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.|University of Colorado Cancer Center, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.
Komal
K
Raina
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.|University of Colorado Cancer Center, University of Colorado Denver Anschutz Medical Campus, Aurora, United States.
Rajesh
R
Agarwal
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D007334:Insulin-Like Growth Factor I
Pancreatic cancer; chemoprevention; chemotherapeutics; drug candidates; natural/dietary agents; signaling pathways.