Four individually druggable MET hotspots mediate HGF-driven tumor progression
نویسندگان
چکیده
منابع مشابه
Four individually druggable MET hotspots mediate HGF-driven tumor progression.
Activation of MET by HGF plays a key role in tumor progression. Using a recently developed llama platform that generates human-like immunoglobulins, we selected 68 different antibodies that compete with HGF for binding to MET. HGF-competing antibodies recognized 4 distinct hotspots localized in different MET domains. We identified 1 hotspot that coincides with the known HGF β chain binding site...
متن کاملHGF - MET and angiogenesis
1. Abstract 2. Significance of HGF-Met in molecular target therapy of cancer 3. NK4 as HGF-antagonist 4. Biological activity of NK4 as angiogenesis inhibitor 5. Experimental cancer treatment by gene expression of NK4 5.1. Inhibition of invasion-metastasis associated with Met inactivation by NK4 gene therapy 5.2. NK4 gene therapy using recombinant adenovirus for metastatic cancers 6. Conclusion ...
متن کاملLY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth.
PURPOSE MET, the receptor for hepatocyte growth factor (HGF), has been implicated in driving tumor proliferation and metastasis. High MET expression is correlated with poor prognosis in multiple cancers. Activation of MET can be induced either by HGF-independent mechanisms such as gene amplification, specific genetic mutations, and transcriptional upregulation or by HGF-dependent autocrine or p...
متن کاملHGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation
Tumor metastases are responsible for approximately 90% of all cancer-related deaths. Metastasis formation is a multistep process that requires acquisition by tumor cells of a malignant phenotype that allows them to escape from the primary tumor site and invade other organs. Each step of this mechanism involves a deep crosstalk between tumor cells and their microenvironment where the host cells ...
متن کاملDepleting MET-Expressing Tumor Cells by ADCC Provides a Therapeutic Advantage over Inhibiting HGF/MET Signaling.
Hepatocyte growth factor (HGF) and its receptor MET represent validated targets for cancer therapy. However, HGF/MET inhibitors being explored as cancer therapeutics exhibit cytostatic activity rather than cytotoxic activity, which would be more desired. In this study, we engineered an antagonistic anti-MET antibody that, in addition to blocking HGF/MET signaling, also kills MET-overexpressing ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Clinical Investigation
سال: 2014
ISSN: 0021-9738
DOI: 10.1172/jci72316