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Review
. 2021 Mar 19:9:664816.
doi: 10.3389/fcell.2021.664816. eCollection 2021.

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

Siyuan Luan  1 , Xiaoxi Zeng  2 , Chao Zhang  2 , Jiajun Qiu  2 , Yushang Yang  1 , Chengyi Mao  1 , Xin Xiao  1 , Jianfeng Zhou  1 , Yonggang Zhang  3   4 , Yong Yuan  1
Affiliations
Review

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

Siyuan Luan et al. Front Cell Dev Biol. .

Abstract

Drug resistance represents the major obstacle to get the maximum therapeutic benefit for patients with esophageal cancer since numerous patients are inherently or adaptively resistant to therapeutic agents. Notably, increasing evidence has demonstrated that drug resistance is closely related to the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic and ever-changing complex biological network whose diverse cellular and non-cellular components influence hallmarks and fates of tumor cells from the outside, and this is responsible for the development of resistance to conventional therapeutic agents to some extent. Indeed, the formation of drug resistance in esophageal cancer should be considered as a multifactorial process involving not only cancer cells themselves but cancer stem cells, tumor-associated stromal cells, hypoxia, soluble factors, extracellular vesicles, etc. Accordingly, combination therapy targeting tumor cells and tumor-favorable microenvironment represents a promising strategy to address drug resistance and get better therapeutic responses for patients with esophageal cancer. In this review, we mainly focus our discussion on molecular mechanisms that underlie the role of TME in drug resistance in esophageal cancer. We also discuss the opportunities and challenges for therapeutically targeting tumor-favorable microenvironment, such as membrane proteins, pivotal signaling pathways, and cytokines, to attenuate drug resistance in esophageal cancer.

Keywords: chemoresistance; chemotherapy; drug resistance; esophageal cancer; immunotherapy; targeted therapy; therapeutic response; tumor microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Resistance mechanisms of cellular components, including (A) cancer stem cells, (B) cancer-associated fibroblasts, and (C) immune inflammatory cells, in the tumor microenvironment in EC.
FIGURE 2
FIGURE 2
Resistance mechanisms of non-cellular components in the tumor microenvironment in EC.
See this image and copyright information in PMC

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