Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review

Cell Communication and Signaling

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[1] 0000 0000 8744 8924, grid.268505.c, College of Pharmaceutical Science, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, 310053, Hangzhou, Zhejiang, China;0000 0004 1808 0985, grid.417397.f, Zhejiang Cancer Hospital, 310022, Hangzhou, China;0000 0004 1760 7474, grid.469171.c, Shanxi Institute of Traditional Chinese Medicine, 030012, Taiyuan, China;0000 0004 1808 0985, grid.417397.f, Zhejiang Cancer Hospital, 310022, Hangzhou, China;School of Pharmacy, Naval Medical University, 325 Guohe Road, Yangpu District, 200433, Shanghai, China;0000 0001 2372 7462, grid.412540.6, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;

关键词: Keap1;    Nrf2;    Pancreatic cancer;    Tumor-suppressive and promoting roles;    Small molecule activators and inhibitors;    Prevention and therapy;   

DOI  :  10.1186/s12964-019-0435-2

来源: publisher

【 摘 要 】

Pancreatic cancer (PC) is one of the most fatal diseases with a very high rate of metastasis and low rate of survival. Despite the advances in understanding this devastating disease, PC still accounts for 3% of all cancers and causes almost 7% of death of cancer patients. Recent studies have demonstrated that the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) and its key negative regulator Kelch-like ECH-associated protein 1 (Keap1) are dysregulated in PC and the Keap1-Nrf2 pathway is an emerging target for PC prevention and therapy. Indeed, Nrf2 plays an either tumor-suppressive or promoting function in PC, which depends on the developmental stages of the disease and the cellular context. Several natural-product Nrf2 activators have been developed to prevent pancreatic carcinogenesis, while the Nrf2 inhibitors have been examined for their efficacy in inhibiting PC growth and metastasis and reversing chemoresistance. However, further preclinical and clinical studies for determining the effectiveness and safety of targeting the Keap1-Nrf2 pathway for PC prevention and therapy are warranted. In this review, we comprehensively discuss the dual roles of the Keap1-Nrf2 signaling pathway in PC as well as the current targeting strategies and known activators and inhibitors of Nrf2. We also propose new strategies that may be used to address the current issues and develop more specific and more effective Nrf2 activator/inhibitors for PC prevention and therapy.

【 授权许可】

CC BY