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Ref Type Journal Article
PMID (25060520)
Authors Ostapoff KT, Cenik BK, Wang M, Ye R, Xu X, Nugent D, Hagopian MM, Topalovski M, Rivera LB, Carroll KD, Brekken RA
Title Neutralizing murine TGFβR2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis.
Journal Vol Issue Date Pages Journal Short Title
Cancer research 74 18 2014 Sep 15 4996-5007 Cancer Res
URL
Abstract Text Elevated levels of TGFβ are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFβ pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFβ remains challenging because TGFβ has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization of TGFβ promotes tumor progression of genetic murine models of pancreatic cancer. Here, we report that neutralizing the activity of murine TGFβ receptor 2 using a monoclonal antibody (2G8) has potent antimetastatic activity in orthotopic human tumor xenografts, syngeneic tumors, and a genetic model of pancreatic cancer. 2G8 reduced activated fibroblasts, collagen deposition, microvessel density, and vascular function. These stromal-specific changes resulted in tumor cell epithelial differentiation and a potent reduction in metastases. We conclude that TGFβ signaling within stromal cells participates directly in tumor cell phenotype and pancreatic cancer progression. Thus, strategies that inhibit TGFβ-dependent effector functions of stromal cells could be efficacious for the therapy of pancreatic tumors. Cancer Res; 74(18); 4996-5007. ©2014 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
2G8 2G8 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
2G8 murine TGFRB2 antibody TGFBR2 Antibody 3 2G8 is a monoclonal antibody that targets murine TGFBR2, potentially resulting in decreased tumor cell proliferation (PMID: 25060520).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References