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Review
. 2021 Nov 15;13(11):1648-1667.
doi: 10.4251/wjgo.v13.i11.1648.

Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers

Xiaoqun Lv  1 , Guoxiong Xu  2
Affiliations
Review

Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers

Xiaoqun Lv et al. World J Gastrointest Oncol. .

Abstract

Gastrointestinal (GI) cancer, including esophageal, gastric, and colorectal cancer, is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths. Despite significant advances in therapeutic strategies for GI cancers in recent decades, drug resistance with various mechanisms remains the prevailing cause of therapy failure in GI cancers. Accumulating evidence has demonstrated that the transforming growth factor (TGF)-β signaling pathway has crucial, complex roles in many cellular functions related to drug resistance. This review summarizes current knowledge regarding the role of the TGF-β signaling pathway in the resistance of GI cancers to conventional chemotherapy, targeted therapy, immunotherapy, and traditional medicine. Various processes, including epithelial-mesenchymal transition, cancer stem cell development, tumor microenvironment alteration, and microRNA biogenesis, are proposed as the main mechanisms of TGF-β-mediated drug resistance in GI cancers. Several studies have already indicated the benefit of combining antitumor drugs with agents that suppress the TGF-β signaling pathway, but this approach needs to be verified in additional clinical studies. Moreover, the identification of potential biological markers that can be used to predict the response to TGF-β signaling pathway inhibitors during anticancer treatments will have important clinical implications in the future.

Keywords: Cancer stem cells; Drug resistance; Epithelial-mesenchymal transition; Gastrointestinal cancer; MicroRNAs; Transforming growth factor-β.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no conflicting interests.

Figures

Figure 1
Figure 1
Mechanisms of transforming growth factor-β signaling and involvement in gastrointestinal cancer chemoresistance. CAFs: Cancer-associated fibroblasts; CSCs: Cancer stem cells; EMT: Epithelial-mesenchymal transition; MSCs: Mesenchymal stem cells; TβRI: TGF-β Type 1 receptor; TβRII: TGF-β Type 2 receptor.
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