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Hypoxia and Tumors

Hypoxia and Tumors © royaltystockphoto / FotoliaGuest Editors: Gabriella D’Orazi1, Donatella Del Bufalo& Maria Carla Bosco3

1 - University “G. D’Annunzio”, Chieti, Italy
2 - IRCCS Regina Elena National Cancer Institute, Rome, Italy
3 - IRCCS Giannina Gaslini Institute, Genova, Italy

Submission deadline: 31st  March 2021. Submit your research here.

Human solid tumors are invariably less well-oxygenated than the normal tissues from which they arose. The cellular response to insufficient tissue oxygenation, or hypoxia, is mainly mediated by the hypoxia-inducible factor (HIF) family of transcription factors. These regulate the expression of multiple genes involved in processes that drive the adaptation and progression of cancer cells, as suggested by experimental and clinical data form various tumor types. 

Hypoxia leads to resistance to radiotherapy and anticancer chemotherapy, increases angiogenesis and vasculogenesis predisposing to tumor metastases, and contributes to altered metabolism and genomic instability. Tumor hypoxia profoundly changes the interaction and cross-talk of cancer cells with the surrounding tumor microenvironment, leading also to immune-resistance and immune-suppression, which help tumor cells to escape from immune surveillance. 

Therefore, given its central role in tumor progression and resistance to therapies, tumor hypoxia is considered a valid target to be exploited in oncology. Several approaches for targeting hypoxic tumor cells have been proposed in recent years, including hypoxia-activated prodrugs, gene therapy, recombinant anaerobic bacteria, specific targeting of HIFs, or targeting pathways important in hypoxic cells such as the mTOR and UPR (unfolded protein response) pathways. Better understanding of hypoxic phenomenon and dissecting out the hypoxia-inducible responses and signaling pathways will grant numerous novel targets in the near future.

The purpose of this thematic series, published in Journal of Experimental & Clinical Cancer Research, is to highlight significant findings and advances in our understanding of the role of the tumor hypoxia in cancer biology and therapy, in light of the 2019 Nobel Prize in Medicine awarded to William G. Kaelin Jr., Sir Peter J. Radcliff and Gregg G. Semenza, whose discoveries contributed to a great understanding to the cell adaptation to reduced oxygen availability.

Keywords: Hypoxia, HIF, Angiogenesis, Invasion and Metastasis, Immune response, Metabolic reprogramming, Microenvironment, Innovative therapies. 

The Special Issue will accept Research Articles and Reviews regarding the latest highlights on the role of hypoxia in all aspects of tumor progression, including therapy resistance and metastases. Please note that all manuscripts submitted to this series, will undergo the standard procedure of external peer review.


  1. Long non-coding RNAs (lncRNAs) are widely involved in human cancers’ progression by regulating tumor cells’ various malignant behaviors. MAPKAPK5-AS1 has been recognized as an oncogene in colorectal cancer. Ho...

    Authors: Liang Wang, Liankang Sun, Runkun Liu, Huanye Mo, Yongshen Niu, Tianxiang Chen, Yufeng Wang, Shaoshan Han, Kangsheng Tu and Qingguang Liu

    Citation: Journal of Experimental & Clinical Cancer Research 2021 40:72

    Content type: Research

    Published on:

  2. The poor prognosis of advanced HCC and limited efficacy of current systemic treatments emphasize the need for new or combined targeted therapies. The development of HCC is a multistage process in which liver i...

    Authors: Astrid Vandierendonck, Helena Degroote, Bart Vanderborght, Xavier Verhelst, Anja Geerts, Lindsey Devisscher and Hans Van Vlierberghe

    Citation: Journal of Experimental & Clinical Cancer Research 2021 40:40

    Content type: Research

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  3. Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and ...

    Authors: Fangyu Chen, Bing Xu, Jie Li, Xi Yang, Junjie Gu, Xijuan Yao and Xinchen Sun

    Citation: Journal of Experimental & Clinical Cancer Research 2021 40:38

    Content type: Research

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  4. Solid tumors often grow in a micro-environment characterized by < 2% O2 tension. This condition, together with the aberrant activation of specific oncogenic patwhays, increases the amount and activity of the hypo...

    Authors: Muhlis Akman, Dimas Carolina Belisario, Iris Chiara Salaroglio, Joanna Kopecka, Massimo Donadelli, Enrico De Smaele and Chiara Riganti

    Citation: Journal of Experimental & Clinical Cancer Research 2021 40:28

    Content type: Review

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  5. With the success of immune checkpoint inhibitors (ICIs), significant progress has been made in the field of cancer immunotherapy. Despite the long-lasting outcomes in responders, the majority of patients with ...

    Authors: Bin Wang, Qin Zhao, Yuyu Zhang, Zijing Liu, Zhuangzhuang Zheng, Shiyu Liu, Lingbin Meng, Ying Xin and Xin Jiang

    Citation: Journal of Experimental & Clinical Cancer Research 2021 40:24

    Content type: Review

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  6. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress....

    Authors: Jianyong Sun, Yanlu Xiong, Kuo Jiang, Bo Xin, Tongtong Jiang, Renji Wei, Yuankang Zou, Hong Tan, Tao Jiang, Angang Yang, Lintao Jia and Lei Wang

    Citation: Journal of Experimental & Clinical Cancer Research 2021 40:12

    Content type: Research

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  7. The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved i...

    Authors: Hong Wu, Tao Wang, Yiqiang Liu, Xin Li, Senlin Xu, Changtao Wu, Hongbo Zou, Mianfu Cao, Guoxiang Jin, Jinyi Lang, Bin Wang, Baohua Liu, Xiaolin Luo and Chuan Xu

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:274

    Content type: Research

    Published on:

  8. Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normo...

    Authors: Tiansheng Li, Chao Mao, Xiang Wang, Ying Shi and Yongguang Tao

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:224

    Content type: Review

    Published on:

  9. Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular f...

    Authors: Xiaoxun Wang, Xiaofang Che, Yang Yu, Yu Cheng, Ming Bai, Zichang Yang, Qiqiang Guo, Xiaochen Xie, Danni Li, Min Guo, Kezuo Hou, Wendong Guo, Xiujuan Qu and Liu Cao

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:221

    Content type: Research

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  10. High-grade gliomas (HGGs), including glioblastoma and diffuse intrinsic pontine glioma, are amongst the most fatal brain tumors. These tumors are associated with a dismal prognosis with a median survival of le...

    Authors: Faiqa Mudassar, Han Shen, Geraldine O’Neill and Eric Hau

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:208

    Content type: Review

    Published on:

  11. Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment—composed of tumor ce...

    Authors: Xianjie Jiang, Jie Wang, Xiangying Deng, Fang Xiong, Shanshan Zhang, Zhaojian Gong, Xiayu Li, Ke Cao, Hao Deng, Yi He, Qianjin Liao, Bo Xiang, Ming Zhou, Can Guo, Zhaoyang Zeng, Guiyuan Li…

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:204

    Content type: Review

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  12. Hypoxia plays a relevant role in tumor-related inflammation toward the metastatic spread and cancer aggressiveness. The pro-inflammatory cytokine interleukin-1β (IL-β) and its cognate receptor IL1R1 contribute...

    Authors: Rosamaria Lappano, Marianna Talia, Francesca Cirillo, Damiano Cosimo Rigiracciolo, Domenica Scordamaglia, Rita Guzzi, Anna Maria Miglietta, Ernestina Marianna De Francesco, Antonino Belfiore, Andrew H. Sims and Marcello Maggiolini

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:153

    Content type: Research

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  13. Hypoxia, a fundamental characteristic of glioma, is considered to promote tumor malignancy by inducing process of epithelial mesenchymal transition (EMT). Ferritin Light Chain (FTL) is one of the iron metaboli...

    Authors: Junhui Liu, Lun Gao, Na Zhan, Pengfei Xu, Ji’an Yang, Fan’en Yuan, Yang Xu, Qiang Cai, Rongxin Geng and Qianxue Chen

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:137

    Content type: Research

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  14. Radiotherapy is the cornerstone of treatment of high-grade gliomas (HGGs). It eradicates tumor cells by inducing oxidative stress and subsequent DNA damage. Unfortunately, almost all HGGs recur locally within ...

    Authors: Han Shen, Kristina Cook, Harriet E. Gee and Eric Hau

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:129

    Content type: Review

    Published on:

  15. Hypoxia-induced alternative splicing is a potent driving force in tumour pathogenesis and progression. In this review, we update currents concepts of hypoxia-induced alternative splicing and how it influences ...

    Authors: Antonietta Rosella Farina, Lucia Cappabianca, Michela Sebastiano, Veronica Zelli, Stefano Guadagni and Andrew Reay Mackay

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:110

    Content type: Review

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  16. Chemo-resistance of bladder cancer has been considered to be one of the serious issues to be solved. In this study, we revealed pivotal role of miR-424 in the regulation of CDDP sensitivity of bladder cancer c...

    Authors: Meng Yu, Toshinori Ozaki, Dan Sun, Haotian Xing, Baojun Wei, Jun An, Jieping Yang, Ying Gao, Shuangjie Liu, Chuize Kong and Yuyan Zhu

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:108

    Content type: Research

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  17. Therapeutic options for patients with hepatocellular carcinoma (HCC) are limited. Transarterial chemoembolization (TACE) is an interventional procedure used to deliver chemotherapy and embolizing agents direct...

    Authors: Sean P. Martin, Valerie Fako, Hien Dang, Dana A. Dominguez, Subreen Khatib, Lichun Ma, Haiyang Wang, Wei Zheng and Xin Wei Wang

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:99

    Content type: Research

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  18. The heterogeneous tumor microenvironment (TME) is highly complex and not entirely understood. These complex configurations lead to the generation of oxygen-deprived conditions within the tumor niche, which mod...

    Authors: Somshuvra Bhattacharya, Kristin Calar and Pilar de la Puente

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:75

    Content type: Review

    Published on:

  19. Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as e...

    Authors: Shiming Tan, Longzheng Xia, Pin Yi, Yaqian Han, Lu Tang, Qing Pan, Yutong Tian, Shan Rao, Linda Oyang, Jiaxin Liang, Jinguan Lin, Min Su, Yingrui Shi, Deliang Cao, Yujuan Zhou and Qianjin Liao

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:67

    Content type: Review

    Published on:

  20. Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA...

    Authors: Lifa Huang, Xu Li, Hui Ye, Yajun Liu, Xiaolong Liang, Chao Yang, Lin Hua, Zhaoxian Yan and Xin Zhang

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:63

    Content type: Research

    Published on:

  21. We have previously described CLDN6 as a tumor suppressor gene in breast cancer. Here, a new finding is that CLDN6 was upregulated under hypoxia, a commonly recognized factor that promotes tumor metastasis. In ...

    Authors: Yiyang Jia, Yantong Guo, Qiu Jin, Huinan Qu, Da Qi, Peiye Song, Xiaoli Zhang, Xinqi Wang, Wenhong Xu, Yuan Dong, Yingying Liang and Chengshi Quan

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:42

    Content type: Research

    Published on:

  22. Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcr...

    Authors: Xiafeng Peng, Han Gao, Rui Xu, Huiyu Wang, Jie Mei and Chaoying Liu

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:27

    Content type: Review

    Published on:

    The Correction to this article has been published in Journal of Experimental & Clinical Cancer Research 2020 39:45

  23. Low oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and radio-therapy, selecting a more maligna...

    Authors: Maria Carla Bosco, Gabriella D’Orazi and Donatella Del Bufalo

    Citation: Journal of Experimental & Clinical Cancer Research 2020 39:8

    Content type: Commentary

    Published on:

    The Correction to this article has been published in Journal of Experimental & Clinical Cancer Research 2020 39:43