ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
TGFβ1 inhibition increases the radiosensitivity of breast cancer cells in vitro and promotes tumor control by radiation in vivo.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 237 citations in OpenAlex.
- Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort: Results from the Randomized SweBCG91RT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients.Journal for immunotherapy of cancer · 2019Trial
- Focal Irradiation and Systemic TGFβ Blockade in Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- RNF113A Promotes Colorectal Cancer Metastasis by Regulating TGF-β Pathway and EMT via Ubiquitin-Mediated Degradation of SNIP1.Balkan medical journal · 2026Article
- Spatially fractionated radiotherapy and immunotherapy: a synergistic strategy for systemic anti-tumor immunity.Journal of translational medicine · 2026Review
- FLASH radiotherapy as an emerging paradigm in radioimmunotherapy: biological rationale, preclinical evidence, and translational roadmap.Frontiers in immunology · 2026Review
- Mitigating radioresistance mechanisms by polymer-lipid manganese dioxide nanoparticles enhances immunogenic cell death and antitumor immune response to facilitate abscopal effect in breast tumor models.Drug delivery and translational research · 2026Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance.Cells · 2025Review
- Bispecific Antibody Targeting VEGF/TGF-β Synergizes with Local Radiotherapy: Turning Tumors from Cold to Inflamed and Amplifying Abscopal Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response.Nature reviews. Cancer · 2025Review
- Exploring the Role of the TGF-β Signaling Pathway in Colorectal Precancerous Polyps Biochemical Genetics.Biochemical genetics · 2025Review
- Radiotherapy as salvage therapy and an adjunct to immunotherapy: exploring local and abscopal mechanisms to overcome immunotherapy resistance: a narrative review.Translational lung cancer research · 2025Review
- Comprehensive review of the resistance mechanisms of colorectal cancer classified by therapy type.Frontiers in immunology · 2025Review
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
- Comparative Glycoproteomic Analysis of Mouse 4T1 Breast Cancer Model.Current medicinal chemistry · 2025Article
- Modulation of Chemotherapy Sensitivity of Breast Cancer Cells through Transforming Growth Factor-beta Pathway-mediated Alterations in DNA Damage Response.International journal of medical sciences · 2025Article
- Review
- PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling.Cellular and molecular life sciences : CMLS · 2024Article
- DNA Double Strand Break and Response Fluorescent Assays: Choices and Interpretation.International journal of molecular sciences · 2024Review
79 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo determine whether inhibition of TGFβ signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. EXPERIMENTAL
designTGFβ-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDA-MB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment with LY364947, a small molecule inhibitor of the TGFβ type I receptor kinase. The DNA damage response was assessed in irradiated MDA-MB-231 cells pretreated with LY364947 in vitro and LY2109761, a pharmacokinetically stable inhibitor of TGFβ signaling, in vivo. The in vitro response of a syngeneic murine tumor, 4T1, was tested using a TGFβ neutralizing antibody, 1D11, with single or fractionated radiation doses in vivo.
resultsHuman breast cancer cell lines pretreated with TGFβ small molecule inhibitor were radiosensitized, irrespective of sensitivity to TGFβ growth inhibition. Consistent with increased clonogenic cell death, radiation-induced phosphorylation of H2AX and p53 was significantly reduced in MDA-MB-231 triple-negative breast cancer cells when pretreated in vitro or in vivo with a TGFβ type I receptor kinase inhibitor. Moreover, TGFβ neutralizing antibodies increased radiation sensitivity, blocked γH2AX foci formation, and significantly increased tumor growth delay in 4T1 murine mammary tumors in response to single and fractionated radiation exposures.
conclusionThese results show that TGFβ inhibition prior to radiation attenuated DNA damage responses, increased clonogenic cell death, and promoted tumor growth delay, and thus may be an effective adjunct in cancer radiotherapy.
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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.