ArticleMolecular cancer therapeutics2012
Inhibition of TGF-β enhances the in vivo antitumor efficacy of EGF receptor-targeted therapy.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 75 citations in OpenAlex.
- Outcomes for FOLFIRI plus bevacizumab or cetuximab in patients treated with oxaliplatin-based adjuvant therapy: A combined analysis of FIRE-3 and CALGB/SWOG 80405 (Alliance).European journal of cancer (Oxford, England : 1990) · 2025Trial
- A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.International journal of molecular sciences · 2023Trial
- A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma.Oral oncology · 2015Trial
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- Phytochemical, Nutritional and Medicinal Properties of Manihot esculenta Leaves: An Integrated Review of Nutritional and Anticancer Insights.Plant foods for human nutrition (Dordrecht, Netherlands) · 2026Review
- Network-based approach identifies key genes associated with tumor heterogeneity in HPV positive and negative head and neck cancer patients.Scientific reports · 2025Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Therapeutic potential of Bacopa monnieri extracts against hepatocellular carcinoma through in-vitro and computational studies.PloS one · 2025Article
- Review
- Radiomics-based model for prediction of TGF-β1 expression in head and neck squamous cell carcinoma.American journal of nuclear medicine and molecular imaging · 2024Article
- Review
- Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer.Journal of gastrointestinal oncology · 2023Article
- BCA101 Is a Tumor-Targeted Bifunctional Fusion Antibody That Simultaneously Inhibits EGFR and TGFβ Signaling to Durably Suppress Tumor Growth.Cancer research · 2023Article
- Association Study of Transforming Growth Factor Beta 1 + 29 T/C exon 1 Polymorphism in Breast Cancer Patients from North Indian Population.Applied biochemistry and biotechnology · 2023Article
- The interplay of cytokine signaling and non-coding RNAs in head and neck squamous cell carcinoma pathobiology.Molecular biology reports · 2022Review
- Mucinous Histology Is Associated with Resistance to Anti-EGFR Therapy in Patients with Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer.The oncologist · 2022Article
- Exploiting Canonical TGFβ Signaling in Cancer Treatment.Molecular cancer therapeutics · 2022Review
- Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis.Scientific reports · 2021Article
- Association between Altered Oncogenic Signaling Pathways and Overall Survival of Patients with Metastatic Colorectal Cancer.Diagnostics (Basel, Switzerland) · 2021Article
- Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.Oral oncology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
EGF receptor (EGFR)-targeted monoclonal antibodies (mAb), such as cetuximab, execute their antitumor effect in vivo via blockade of receptor-ligand interactions and engagement of Fcγ receptors on immune effector cells that trigger antibody-dependent cell-mediated cytotoxicity (ADCC). We show that tumors counteract the in vivo antitumor activity of anti-EGFR mAbs by increasing tumor cell-autonomous expression of TGF-β. We show that TGF-β suppresses the expression of key molecular effectors of immune cell-mediated cytotoxicity, including Apo2L/TRAIL, CD95L/FasL, granzyme B, and IFN-γ. In addition to exerting an extrinsic inhibition of the cytotoxic function of immune effectors, TGF-β-mediated activation of AKT provides an intrinsic EGFR-independent survival signal that protects tumor cells from immune cell-mediated apoptosis. Treatment of mice-bearing xenografts of human head and neck squamous cell carcinoma with cetuximab resulted in emergence of resistant tumor cells that expressed relatively higher levels of TGF-β compared with untreated tumor-bearing mice. Although treatment with cetuximab alone forced the natural selection of TGF-β-overexpressing tumor cells in nonregressing tumors, combinatorial treatment with cetuximab and a TGF-β-blocking antibody prevented the emergence of such resistant tumor cells and induced complete tumor regression. Therefore, elevated levels of TGF-β in the tumor microenvironment enable tumor cells to evade ADCC and resist the antitumor activity of cetuximab in vivo. Our results show that TGF-β is a key molecular determinant of the de novo and acquired resistance of cancers to EGFR-targeted mAbs, and provide a rationale for combinatorial targeting of TGF-β to improve anti-EGFR-specific antibody therapy of EGFR-expressing cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.