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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

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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References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. - PubMed
    1. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70:145–164. - PubMed
    1. Piawah S, Venook AP. Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer. Cancer. 2019;125:4139–4147. - PubMed
    1. Chu JN, Choi J, Ostvar S, Torchia JA, Reynolds KL, Tramontano A, Gainor JF, Chung DC, Clark JW, Hur C. Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Cancer. 2019;125:278–289. - PMC - PubMed
    1. Adlard JW, Richman SD, Seymour MT, Quirke P. Prediction of the response of colorectal cancer to systemic therapy. Lancet Oncol. 2002;3:75–82. - PubMed