Latest therapeutic target for gastric cancer: Anthrax toxin receptor 1

Abstract

Anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8, is a highly conserved cell surface protein overexpressed in tumor-infiltrating vessels. It was first found in vascular endothelial cells of human colorectal cancer. Although our understanding of its physiological function is limited, it has been found that ANTXR1 binds collagen and promotes migration of endothelial cells in vitro . ANTXR1 is upregulated in vessels of different tumor types in mice and humans, and is also expressed by tumor cells themselves in some tumors, such as gastric, lung, intestinal and breast cancer. Developmental angiogenesis and wound healing were not disturbed in ANTXR1 knockout mice, but compared with wild-type mice, growth of melanoma was impaired after ANTXR1 knockout, indicating that host-derived ANTXR1 can promote tumor growth on the basis of immune activity. Previous studies have shown that ANTXR1 vaccines or sublethal doses of anthrax toxin can inhibit angiogenesis, slow tumor growth and prolong survival. These studies suggest that ANTXR1 is necessary for tumor rather than physiological angiogenesis. It has been found that ANTXR1 plays an important role in tumor angiogenesisas well as in the growth and metastasis of many kinds of tumors. This article reviews the physiological function of ANTXR1 and its role in different kinds of cancer.

Hypoxia-related tumor environment correlated with immune infiltration and therapeutic sensitivity in diffuse large B-cell lymphoma

“…ANTXR1 is a receptor for anthrax toxin and is highly expressed in tumor endothelial cells. It has been reported to be an oncogene and plays roles in tumor angiogenesis and in the growth, metastasis, and immunosuppression of many kinds of tumors (Huang et al, 2020;Sun et al, 2021). Its antibody-drug conjugate may facilitate selective destruction of tumor blood vessels yielding enhanced anti-cancer efficacy and reduced normal tissue toxicities (Frankel et al, 2011).…”

AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy

“…The physiological roles of TEM8 and CMG2 are related to the regulation of extracellular matrix homeostasis and remodeling angiogenesis, cell migration, and cell spreading by interacting with the actin cytoskeleton, similar to integrins [ 5 , 61 , 70 ]. These functions may be related to tumor occurrence and metastasis [ 70 ]. Angiogenesis is regulated by interactions with components of the extracellular matrix (ECM).…”

Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics

“…Studies have demonstrated that TEM8/ANTXR1 is enriched in triple negative breast cancer (Xu et al, 2021), prostate cancer (Li et al, 2021a), gastric cancer (Li et al, 2021b;Sun et al, 2021), pancreatic cancer (Alcalá et al, 2019), angiosarcoma (Kusaba et al, 2021(Kusaba et al, ), colon cancer (Ł et al, 2021, and non-small cell lung cancer (NSCLC) (Gong et al, 2021). In multiple tumor types, upregulation of TEM8/ ANTXR1 is a negative prognostic indicator (Li et al, 2021a;Ł et al, 2021;Ding et al, 2021).…”

“…However, understanding SVV-001 and the unique tumor microenvironment, represented by upregulation of TEM8/ANTXR1, that it targets, has the potential to provide additional clues about mechanisms of resistance to immunotherapy and chemotherapy in neuroendocrine neoplasms and other cancers. TEM8/ANTXR1 upregulation has been described in a variety of solid tumors types including triple negative breast cancer (Xu et al, 2021), prostate cancer (Li et al, 2021a), gastric cancer (Li et al, 2021b;Sun et al, 2021), pancreatic cancer (Alcalá et al, 2019), angiosarcoma (Kusaba et al, 2021(Kusaba et al, ), colon cancer (Ł et al, 2021, and NSCLC (Gong et al, 2021). Lineage plasticity with a transformation from adenocarcinomas to carcinomas with neuroendocrine differentiation has been described in a variety of solid tumors, including lung and prostate primary tumors (Farrell et al, 2017;Rubin et al, 2020;Ito et al, 2021).…”