ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
The Outcome of TGFβ Antagonism in Metastatic Breast Cancer Models
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 25 citations in OpenAlex.
- Tumoral pSMAD2 as a prognostic biomarker in early-stage breast cancer: insights from the randomized SweBCG91RT trial.Breast cancer research and treatment · 2025Trial
- Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.Journal for immunotherapy of cancer · 2021Trial
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Key regulatory elements of the TGFβ-LRRC15 axis predict disease progression and immunotherapy resistance across cancer types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Blockade of Tumor-Intrinsic TGFβ Signaling Drives Hyperprogression in Small Cell Lung Cancer.Cancer discovery · 2026Article
- Cancer stem cells are hyper-responsive sensors of the tumour microenvironment and regulate metastasis dynamics through YAP/TAZ.Nature cell biology · 2026Article
- Prognostic RNA-splicing archetypes in breast cancer identified by extended pre-training of histopathology foundation models.Nature communications · 2026Article
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response.Nature reviews. Cancer · 2025Review
- The role of collagen and collagen I/III ratio in pathological conditions: insights into molecular mechanisms and therapeutic approaches.Frontiers in bioengineering and biotechnology · 2025Review
- Role of TGFβ-activated cancer-associated fibroblasts in the resistance to checkpoint blockade immunotherapy.Frontiers in oncology · 2025Review
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- First pan-specific vNAR against human TGF-β as a potential therapeutic application: in silico modeling assessment.Scientific reports · 2023Article
- Intertumoral Differences Dictate the Outcome of TGF-β Blockade on the Efficacy of Viro-Immunotherapy.Cancer research communications · 2023Article
- Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.PLoS genetics · 2022Article
- Article
- New Advances in Targeted Therapy of HER2-Negative Breast Cancer.Frontiers in oncology · 2022Review
- Exploiting Canonical TGFβ Signaling in Cancer Treatment.Molecular cancer therapeutics · 2022Review
- Systematic investigation of cytokine signaling activity at the tissue and single-cell levels.Nature methods · 2021Article
- TGFβ1 in Cancer-Associated Fibroblasts Is Associated With Progression and Radiosensitivity in Small-Cell Lung Cancer.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTGFβs are overexpressed in many advanced cancers and promote cancer progression through mechanisms that include suppression of immunosurveillance. Multiple strategies to antagonize the TGFβ pathway are in early-phase oncology trials. However, TGFβs also have tumor-suppressive activities early in tumorigenesis, and the extent to which these might be retained in advanced disease has not been fully explored. EXPERIMENTAL
designA panel of 12 immunocompetent mouse allograft models of metastatic breast cancer was tested for the effect of neutralizing anti-TGFβ antibodies on lung metastatic burden. Extensive correlative biology analyses were performed to assess potential predictive biomarkers and probe underlying mechanisms.
resultsHeterogeneous responses to anti-TGFβ treatment were observed, with 5 of 12 models (42%) showing suppression of metastasis, 4 of 12 (33%) showing no response, and 3 of 12 (25%) showing an undesirable stimulation (up to 9-fold) of metastasis. Inhibition of metastasis was immune-dependent, whereas stimulation of metastasis was immune-independent and targeted the tumor cell compartment, potentially affecting the cancer stem cell. Thus, the integrated outcome of TGFβ antagonism depends on a complex balance between enhancing effective antitumor immunity and disrupting persistent tumor-suppressive effects of TGFβ on the tumor cell. Applying transcriptomic signatures derived from treatment-naïve mouse primary tumors to human breast cancer datasets suggested that patients with breast cancer with high-grade, estrogen receptor-negative disease are most likely to benefit from anti-TGFβ therapy.
conclusionsContrary to dogma, tumor-suppressive responses to TGFβ are retained in some advanced metastatic tumors. Safe deployment of TGFβ antagonists in the clinic will require good predictive biomarkers.
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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.