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Chemoprevention strategies for pancreatic cancer

Abstract

Pancreatic cancer has a poor prognosis and is often diagnosed at an advanced stage, which makes it difficult to treat. The low survival rate of patients with pancreatic cancer points towards an increased need for novel therapeutic and chemopreventive strategies and also early detection of this disease. Increased consumption of fruits and vegetables has been associated with a reduced risk of pancreatic cancer. Synthetic and natural, diet-derived bioactive compounds have been evaluated as pancreatic cancer chemopreventive agents and have demonstrated various degrees of efficacy in cellular and in vivo animal models. Some chemopreventive agents (for example, curcumin or resveratrol) have also been reported to sensitize pancreatic cancer cells to standard chemotherapeutic drugs (for example, gemcitabine or erlotinib), which suggests that chemopreventive agents could potentially be used as potentiators of standard chemotherapy. Few clinical trials of pancreatic cancer chemopreventive agents have been completed and some are in early phases. Further development of pancreatic cancer chemopreventive agents may prove to be tremendously valuable for individuals at high risk of developing pancreatic cancer and patients who present with premalignant lesions. This Review discusses the current state of the pancreatic cancer chemoprevention field and highlights the challenges ahead.

Key Points

  • Pancreatic cancer has a low survival rate, which has not improved in the past few decades; current chemotherapeutic treatment is not effective

  • A great deal of research interest has been directed towards evaluating natural and synthetic chemopreventive agents in cellular and animal models of pancreatic cancer

  • Few pancreatic cancer clinical trials with chemopreventive agents have been completed; more trials are in early phases

  • Pancreatic cancer chemopreventive agents could be useful for individuals who are at high risk of developing cancer or who present with premalignant lesions

  • Pancreatic cancer chemopreventive agents have a potential use as potentiators of standard chemotherapy

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Figure 1: Examples of molecular targets in pancreatic cancer that are downregulated or upregulated by chemopreventive agents.

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Acknowledgements

This work was supported in part by funds from Shirley Hobbs Martin Memorial Fund (awarded to R. E. Brand) and the National Cancer Institute grant R01CA101753 (awarded to S. V. Singh). We thank D. C. Whitcomb for helpful suggestions and feedback on the manuscript. We apologize to the investigators whose work could not be cited due to space limitations.

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Correspondence to Silvia D. Stan.

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Stan, S., Singh, S. & Brand, R. Chemoprevention strategies for pancreatic cancer. Nat Rev Gastroenterol Hepatol 7, 347–356 (2010). https://doi.org/10.1038/nrgastro.2010.61

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