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The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment

SIMPLE SUMMARY: Developing therapeutic resistance to monoclonal antibodies (mAbs) causes increasing failure in oral squamous cell carcinoma (OSCC) treatment. A clear understanding of the molecular basis for drug resistance will pave the way for OSCC management and a new effective therapeutic modalit...

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Autores principales: Bai, Yunpeng, Sha, Jingjing, Okui, Tatsuo, Moriyama, Ichiro, Ngo, Huy Xuan, Tatsumi, Hiroto, Kanno, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657021/
https://www.ncbi.nlm.nih.gov/pubmed/34885013
http://dx.doi.org/10.3390/cancers13235905
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author Bai, Yunpeng
Sha, Jingjing
Okui, Tatsuo
Moriyama, Ichiro
Ngo, Huy Xuan
Tatsumi, Hiroto
Kanno, Takahiro
author_facet Bai, Yunpeng
Sha, Jingjing
Okui, Tatsuo
Moriyama, Ichiro
Ngo, Huy Xuan
Tatsumi, Hiroto
Kanno, Takahiro
author_sort Bai, Yunpeng
collection PubMed
description SIMPLE SUMMARY: Developing therapeutic resistance to monoclonal antibodies (mAbs) causes increasing failure in oral squamous cell carcinoma (OSCC) treatment. A clear understanding of the molecular basis for drug resistance will pave the way for OSCC management and a new effective therapeutic modality. This review elucidates the role played by EMT during the emergence of mAbs resistance and the configuration of the tumor microenvironment. The cancer cells that undergo the EMT process also cause significant energy substrate consumption which leads to a limited number and function of effective T-cells, eventually leading to immune evasion. This review firstly reveals the implicit crosstalk between the EMT, energy metabolism, and therapeutic resistance of mAbs. A focus on the rebalanced energy homeostasis in cancer cells and T-cells may provide a new perspective on the treatment of OSCC. ABSTRACT: Oral squamous cell carcinoma (OSCC) is a major type of cancer that accounts for over 90% of all oral cancer cases. Recently developed evidence-based therapeutic regimens for OSCC based on monoclonal antibodies (mAbs), such as cetuximab, pembrolizumab, and nivolumab, have attracted considerable attention worldwide due to their high specificity, low toxicity, and low rates of intolerance. However, the efficacy of those three mAbs remains poor because of the low rate of responders and acquired resistance within a short period of time. The epithelial–mesenchymal transition (EMT) process is fundamental for OSCC growth and metastasis and is also responsible for the poor response to mAbs. During EMT, cancer cells consume abundant energy substrates and create an immunosuppressive tumor microenvironment to support their growth and evade T cells. In this review, we provide an overview of the complex roles of major substrates and signaling pathways involved in the development of therapeutic resistance in OSCC. In addition, we summarize potential therapeutic strategies that may help overcome this resistance. This review aims to help oral oncologists and researchers aiming to manage OSCC and establish new treatment modalities.
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spelling pubmed-86570212021-12-10 The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment Bai, Yunpeng Sha, Jingjing Okui, Tatsuo Moriyama, Ichiro Ngo, Huy Xuan Tatsumi, Hiroto Kanno, Takahiro Cancers (Basel) Review SIMPLE SUMMARY: Developing therapeutic resistance to monoclonal antibodies (mAbs) causes increasing failure in oral squamous cell carcinoma (OSCC) treatment. A clear understanding of the molecular basis for drug resistance will pave the way for OSCC management and a new effective therapeutic modality. This review elucidates the role played by EMT during the emergence of mAbs resistance and the configuration of the tumor microenvironment. The cancer cells that undergo the EMT process also cause significant energy substrate consumption which leads to a limited number and function of effective T-cells, eventually leading to immune evasion. This review firstly reveals the implicit crosstalk between the EMT, energy metabolism, and therapeutic resistance of mAbs. A focus on the rebalanced energy homeostasis in cancer cells and T-cells may provide a new perspective on the treatment of OSCC. ABSTRACT: Oral squamous cell carcinoma (OSCC) is a major type of cancer that accounts for over 90% of all oral cancer cases. Recently developed evidence-based therapeutic regimens for OSCC based on monoclonal antibodies (mAbs), such as cetuximab, pembrolizumab, and nivolumab, have attracted considerable attention worldwide due to their high specificity, low toxicity, and low rates of intolerance. However, the efficacy of those three mAbs remains poor because of the low rate of responders and acquired resistance within a short period of time. The epithelial–mesenchymal transition (EMT) process is fundamental for OSCC growth and metastasis and is also responsible for the poor response to mAbs. During EMT, cancer cells consume abundant energy substrates and create an immunosuppressive tumor microenvironment to support their growth and evade T cells. In this review, we provide an overview of the complex roles of major substrates and signaling pathways involved in the development of therapeutic resistance in OSCC. In addition, we summarize potential therapeutic strategies that may help overcome this resistance. This review aims to help oral oncologists and researchers aiming to manage OSCC and establish new treatment modalities. MDPI 2021-11-24 /pmc/articles/PMC8657021/ /pubmed/34885013 http://dx.doi.org/10.3390/cancers13235905 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bai, Yunpeng
Sha, Jingjing
Okui, Tatsuo
Moriyama, Ichiro
Ngo, Huy Xuan
Tatsumi, Hiroto
Kanno, Takahiro
The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment
title The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment
title_full The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment
title_fullStr The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment
title_full_unstemmed The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment
title_short The Epithelial–Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment
title_sort epithelial–mesenchymal transition influences the resistance of oral squamous cell carcinoma to monoclonal antibodies via its effect on energy homeostasis and the tumor microenvironment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657021/
https://www.ncbi.nlm.nih.gov/pubmed/34885013
http://dx.doi.org/10.3390/cancers13235905
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