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Efficacy and immune mechanisms of cetuximab for the treatment of metastatic colorectal cancer

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Clinical Oncology and Cancer Research

Abstract

Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor and inhibits downstream intracellular signals. Research has shown that cetuximab can stimulate the autoimmune system and produce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity reactions, which can recruit cytotoxic lymphocytes to attack and kill cancer cells. Cetuximab is mainly indicated for patients with epidermal growth factor receptor-positive metastatic colorectal cancer who fail to respond to both irinotecan- and oxaliplatin-based regimens. The efficacy and safety of cetuximab as monotherapy or in combination with other treatment options were evaluated in a series of phase II and phase III trials. Identifying the clinical and molecular markers that can predict which patient groups may best benefit from cetuximab treatment is key to improving patient outcomes and avoiding unnecessary toxicities and costs. Herein, we discuss the mechanisms of action by which cetuximab exerts its antitumor effects, as well as the possible clinical and molecular markers that may help predict therapeutic benefits for patients with metastatic colorectal cancer.

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Abbreviations

EGFR:

epidermal growth factor receptor

CDC:

complement-dependent cytotoxicity

mCRC:

metastatic colorectal cancer

mAb:

monoclonal antibody

ADCC:

antibody-dependent cellular cytotoxicity

TA:

tumor antigen

EGF:

epidermal growth factor

NK:

natural killer (cells)

DC:

dendritic cells

CTL:

cytotoxic lymphocyte

BSC:

best supportive care

OS:

overall survival

PFS:

progression-free survival

RR:

response rate

APC:

antigenpresenting cell

HLA:

human leukocyte antigen

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Authors and Affiliations

  1. Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China

    Hao Zhuang, Zhen-yi Xue, Lu Wang, Xiao-yan Li, Ning Zhang & Rong-xin Zhang

  2. Department of Immunology, Tianjin Medical University, Tianjin, 300070, China

    Rong-xin Zhang

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  1. Hao Zhuang
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  2. Zhen-yi Xue
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  3. Lu Wang
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Correspondence to Rong-xin Zhang.

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Zhuang, H., Xue, Zy., Wang, L. et al. Efficacy and immune mechanisms of cetuximab for the treatment of metastatic colorectal cancer. Clin. Oncol. Cancer Res. 8, 207–214 (2011). https://doi.org/10.1007/s11805-011-0582-8

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