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Updated: Mar 23, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Neuraminidase-1: a novel therapeutic target in multistage tumorigenesis
Fiona Haxho1, Ronald J Neufeld2, Myron R Szewczuk1
1Departments of Biomedical and Molecular Sciences, Kingston, Ontario, Canada.
Abstract:
Several of the growth factors and their receptor tyrosine kinases (RTK) such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and insulin are promising candidate targets for cancer therapy. Indeed, tyrosine kinase inhibitors (TKI) have been developed to target these growth factors and their receptors, and have demonstrated dramatic initial responses in cancer therapy. Yet, most patients ultimately develop TKI drug resistance and relapse. It is essential in the clinical setting that the targeted therapies are to circumvent multistage tumorigenesis, including genetic mutations at the different growth factor receptors, tumor neovascularization, chemoresistance of tumors, immune-mediated tumorigenesis and the development of tissue invasion and metastasis. Here, we identify a novel receptor signaling platform linked to EGF, NGF, insulin and TOLL-like receptor (TLR) activations, all of which are known to play major roles in tumorigenesis. The importance of these findings signify an innovative and promising entirely new targeted therapy for cancer. The role of mammalian neuraminidase-1 (Neu1) in complex with matrix metalloproteinase-9 and G protein-coupled receptor tethered to RTKs and TLRs is identified as a major target in multistage tumorigenesis. Evidence exposing the link connecting growth factor-binding and immune-mediated tumorigenesis to this novel receptor-signaling paradigm will be reviewed in its current relationship to cancer.
Insights
A novel signaling platform involving growth factors, neuraminidase-1 (Neu1), and Toll-like receptors (TLR) offers a new target for cancer therapy. This discovery aims to overcome drug resistance and address multistage tumorigenesis for improved patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Growth factors and receptor tyrosine kinases (RTKs) are key targets in cancer therapy, with tyrosine kinase inhibitors (TKIs) showing initial success.
- However, most patients develop TKI resistance, necessitating novel therapeutic strategies to combat multistage tumorigenesis.
- Understanding resistance mechanisms, including genetic mutations, neovascularization, chemoresistance, immune evasion, and metastasis, is crucial for effective cancer treatment.
Purpose of the Study:
- To identify a novel receptor signaling platform implicated in tumorigenesis.
- To explore the role of mammalian neuraminidase-1 (Neu1) in cancer development.
- To establish a new therapeutic target for overcoming TKI resistance and treating advanced cancers.
Main Methods:
- The study identifies a novel receptor signaling platform.
- It investigates the role of mammalian neuraminidase-1 (Neu1) in complex with matrix metalloproteinase-9 and G protein-coupled receptors.
- The research links growth factor and Toll-like receptor (TLR) activations to this platform.
Main Results:
- A novel receptor signaling platform linked to epidermal growth factor (EGF), nerve growth factor (NGF), insulin, and Toll-like receptor (TLR) activations was identified.
- Mammalian neuraminidase-1 (Neu1) in complex with matrix metalloproteinase-9 and G protein-coupled receptors tethered to RTKs and TLRs was identified as a major target in multistage tumorigenesis.
- Evidence linking growth factor-binding and immune-mediated tumorigenesis to this novel receptor-signaling paradigm was reviewed.
Conclusions:
- The identified novel receptor signaling platform presents a promising new targeted therapy for cancer.
- Targeting this platform, particularly the Neu1 complex, may circumvent multistage tumorigenesis and overcome TKI drug resistance.
- This discovery offers an innovative approach to cancer treatment by addressing complex mechanisms of tumor development and progression.
