Elevated expression of ANTXR1 gene in tumors is a poor prognostic biomarker for patients with bladder cancer

L. S. Franco1, S. Arunachalam1, A. Chauhan2, S. A. Kareff3 and P. L. Hallenbeck1* 1Seneca Therapeutics, Inc., Blue Bell, PA, United States, 2Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, United States,3Lynn Cancer Institute, Boca Raton Regional Hospital, Boca Raton, FL, United States

The TEM8 protein coded by the ANTXR1 gene represents an emerging biomarker in solid tumors. In addition to the various roles TEM8 plays in oncogenesis, including angiogenesis, epithelial-to-mesenchymal transition, and cell migration, it has also been shown that the overexpression of the ANTXR1 gene in solid tumors correlates with poor prognostic indicators in several solid tumor histologies. As such, TEM8 has been identified as the target of novel oncologic therapies. It is especially attractive given its selective expression on the surface of solid tumor cells and associated stromal cells, such as cancer stem cells, invasive cancer cells, and immune cells, such as macrophages, angiogenic endothelial cells, pericytes, and cancer-associated fibroblasts. Furthermore, TEM8 plays this unique role as a mostly non-mutated gene in solid cancers. Here, we demonstrate that elevated expression of ANTXR1 in bladder cancer showed a statistical difference not only in overall survival (OS) but in progression free survival (PFS), confirming the prognostic biomarker power of ANTXR1 expression.

KEYWORDS
TEM8, prognostic biomarker, bladder cancer, downstream pathway, survival

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TEM8 in Oncogenesis: Protein Biology, Pre-Clinical Agents, and Clinical Rationale

Samuel A Kareff 1, Virginia Corbett 2, Paul Hallenbeck 3, Aman Chauhan 4

Affiliations Expand

• PMID: 37998358

• PMCID: PMC10670355

• DOI: 10.3390/cells12222623

ABSTRACT

The TEM8 protein represents an emerging biomarker in many solid tumor histologies. Given the various roles it plays in oncogenesis, including but not limited to angiogenesis, epithelial-to-mesenchymal transition, and cell migration, TEM8 has recently served and will continue to serve as the target of novel oncologic therapies. We review herein the role of TEM8 in oncogenesis. We review its normal function, highlight the additional roles it plays in the tumor microenvironment, and synthesize pre-clinical and clinical data currently available. We underline the protein's prognostic and predictive abilities in various solid tumors by (1) highlighting its association with more aggressive disease biology and poor clinical outcomes and (2) assessing its associated clinical trial landscape. Finally, we offer future directions for clinical studies involving TEM8, including incorporating pre-clinical agents into clinical trials and combining previously tested oncologic therapies with currently available treatments, such as immunotherapy.

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