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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2021

Open Access 01-12-2021 | Metastasis | Review

Targeting hypoxic tumor microenvironment in pancreatic cancer

Authors: Jinxin Tao, Gang Yang, Wenchuan Zhou, Jiangdong Qiu, Guangyu Chen, Wenhao Luo, Fangyu Zhao, Lei You, Lianfang Zheng, Taiping Zhang, Yupei Zhao

Published in: Journal of Hematology & Oncology | Issue 1/2021

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Abstract

Attributable to its late diagnosis, early metastasis, and poor prognosis, pancreatic cancer remains one of the most lethal diseases worldwide. Unlike other solid tumors, pancreatic cancer harbors ample stromal cells and abundant extracellular matrix but lacks vascularization, resulting in persistent and severe hypoxia within the tumor. Hypoxic microenvironment has extensive effects on biological behaviors or malignant phenotypes of pancreatic cancer, including metabolic reprogramming, cancer stemness, invasion and metastasis, and pathological angiogenesis, which synergistically contribute to development and therapeutic resistance of pancreatic cancer. Through various mechanisms including but not confined to maintenance of redox homeostasis, activation of autophagy, epigenetic regulation, and those induced by hypoxia-inducible factors, intratumoral hypoxia drives the above biological processes in pancreatic cancer. Recognizing the pivotal roles of hypoxia in pancreatic cancer progression and therapies, hypoxia-based antitumoral strategies have been continuously developed over the recent years, some of which have been applied in clinical trials to evaluate their efficacy and safety in combinatory therapies for patients with pancreatic cancer. In this review, we discuss the molecular mechanisms underlying hypoxia-induced aggressive and therapeutically resistant phenotypes in both pancreatic cancerous and stromal cells. Additionally, we focus more on innovative therapies targeting the tumor hypoxic microenvironment itself, which hold great potential to overcome the resistance to chemotherapy and radiotherapy and to enhance antitumor efficacy and reduce toxicity to normal tissues.
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Metadata
Title
Targeting hypoxic tumor microenvironment in pancreatic cancer
Authors
Jinxin Tao
Gang Yang
Wenchuan Zhou
Jiangdong Qiu
Guangyu Chen
Wenhao Luo
Fangyu Zhao
Lei You
Lianfang Zheng
Taiping Zhang
Yupei Zhao
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2021
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-01030-w

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