Transforming growth factor-β: a therapeutic target for cancer

The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells

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TGF-β SIGNAL TRANSDUCTION

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Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease

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<i>DPC4</i> , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1

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TGF-β Signaling in Tumor Suppression and Cancer Progression

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Inactivation of the Type II TGF-β Receptor in Colon Cancer Cells with Microsatellite Instability

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Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling

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Generation of Breast Cancer Stem Cells through Epithelial-Mesenchymal Transition

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TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes

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Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor.

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Balancing the activation state of the endothelium via two distinct TGF‐β type I receptors

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Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism.

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Defective haematopoiesis and vasculogenesis in transforming growth factor-β1 knock out mice

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Smad6 inhibits signalling by the TGF-β superfamily

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Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor β-mediated Epithelial to Mesenchymal Transition and Cell Migration

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CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner

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TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors.

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Transforming growth factor–β3 is required for secondary palate fusion

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Betaglycan presents ligand to the TGFβ signaling receptor

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Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications

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Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer.

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TGF‐β receptor‐activated p38 MAP kinase mediates Smad‐independent TGF‐β responses

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Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells.

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TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells.Preprint

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DPC4 gene in various tumor types.

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Inhibition of Transforming Growth Factor (TGF)-β1–Induced Extracellular Matrix with a Novel Inhibitor of the TGF-β Type I Receptor Kinase Activity: SB-431542

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TGFβ signaling is necessary for carcinoma cell invasiveness and metastasis

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Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix.

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Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway

Lahn, M. M. F., Herbertz, S., Sawyer, J. S., Stauber, A. J., Gueorguieva, I., Driscoll, K. E., Estrem, S. T., Cleverly, A., Desaiah, D., Guba, S. C., et al. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s86621 · Cited by 558 · see citing works

Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.

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Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins

Lasorella, A., Noseda, M., Beyna, M., & Iavarone, A. (2000) · Nature · doi:10.1038/35036504 · Cited by 497 · see citing works

TGFβ influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b

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Phase I study of GC1008 (fresolimumab): a human anti‐transforming growth factor‐beta (TGFβ) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma

Morris, J. C., Tan, A. R., Olencki, T. E., Shapiro, G. I., Dezube, B. J., Reiss, M., Hsu, F. J., Berzofsky, J. A., & Lawrence, D. P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090353 · Cited by 487 · see citing works

Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases

Muraoka, R. S., Dumont, N., Ritter, C. A., Dugger, T. C., Brantley, D. M., Chen, J., Easterly, E., Roebuck, L. R., Ryan, S. T., Gotwals, P. J., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15234 · Cited by 485 · see citing works

Cellular Mechanisms of Fatal Early-Onset Autoimmunity in Mice with the T Cell-Specific Targeting of Transforming Growth Factor-β Receptor

Marie, J. C., Liggitt, D., & Rudensky, A. Y. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.012 · Cited by 480 · see citing works

High TGFβ-Smad Activity Confers Poor Prognosis in Glioma Patients and Promotes Cell Proliferation Depending on the Methylation of the PDGF-B Gene

Bruna, A., Darken, R. S., Rojo, F., Ocaña, A., Peñuelas, S., Arias, A., Parı́s, R., Tortosa, A., Mora, J., Baselga, J. M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.11.023 · Cited by 472 · see citing works

Targeted therapy for high-grade glioma with the TGF- 2 inhibitor trabedersen: results of a randomized and controlled phase IIb study

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p38 mitogen-activated protein kinase is required for TGFβ-mediated fibroblastic transdifferentiation and cell migration

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Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases

Muraoka, R. S., Dumont, N., Ritter, C. A., Dugger, T. C., Brantley, D. M., Chen, J., Easterly, E., Roebuck, L. R., Ryan, S. T., Gotwals, P. J., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215234 · Cited by 415 · see citing works

SD-208, a Novel Transforming Growth Factor β Receptor I Kinase Inhibitor, Inhibits Growth and Invasiveness and Enhances Immunogenicity of Murine and Human Glioma CellsIn vitroandIn vivo

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Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers.

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Phase II Study of Belagenpumatucel-L, a Transforming Growth Factor Beta-2 Antisense Gene-Modified Allogeneic Tumor Cell Vaccine in Non–Small-Cell Lung Cancer

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Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression.

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Molecular mechanisms of action of antisense drugs

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Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression

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Complexities of TGF-β Targeted Cancer Therapy

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LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis

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Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter

Wu, S., Cetinkaya, C., Muñoz-Alonso, M. J., von der Lehr, N., Bahram, F., Beuger, V., Eilers, M., León, J., & Larsson, L. (2003) · Oncogene · doi:10.1038/sj.onc.1206145 · Cited by 314 · see citing works

Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas.

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Frequency of Smad gene mutations in human cancers.

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A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer

Giaccone, G., Bazhenova, L. A., Nemunaitis, J., Tan, M., Juhász, E., Ramlau, R., van den Heuvel, M. M., Lal, R., Kloecker, G. H., Eaton, K. D., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.07.035 · Cited by 279 · see citing works

Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis

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Homozygous deletion map at 18q21.1 in pancreatic cancer.

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Targeting the transforming growth factor-β signaling pathway in human cancer

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Blockade of TGF-β signaling by the TGFβR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma

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Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines.

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The type III TGF-β receptor suppresses breast cancer progression

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Targeting the TGFβ signaling network in human neoplasia

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TGFβ1 Inhibition Increases the Radiosensitivity of Breast Cancer Cells In Vitro and Promotes Tumor Control by Radiation In Vivo

Bouquet, F., Pal, A., Pilones, K. A., Demaria, S., Hann, B. C., Akhurst, R. J., Babb, J. S., Lonning, S. M., DeWyngaert, J. K., Formenti, S. C., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0544 · Cited by 240 · see citing works

An Anti–Transforming Growth Factor β Antibody Suppresses Metastasis via Cooperative Effects on Multiple Cell Compartments

Nam, J., Terabe, M., Mamura, M., Kang, M., Chae, H., Stuelten, C. H., Kohn, E. A., Tang, B., Sabzevari, H., Anver, M. R., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0215 · Cited by 233 · see citing works

Antimetastatic Role of Smad4 Signaling in Colorectal Cancer

Zhang, B., Halder, S. K., Kashikar, N., Cho, Y., Datta, A., Gorden, D. L., & Datta, P. K. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.11.004 · Cited by 221 · see citing works

TGF-β-RI Kinase Inhibitor SD-208 Reduces the Development and Progression of Melanoma Bone Metastases

Mohammad, K. S., Javelaud, D., Fournier, P. G. J., Niewolna, M., McKenna, C. R., Peng, X., Duong, V. H., Dunn, L. K., Mauviel, A., & Guise, T. A. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2651 · Cited by 221 · see citing works

Inhibition of TGF- β 2 with AP 12009 in Recurrent Malignant Gliomas: From Preclinical to Phase I/II Studies

Hau, P., Jachimczak, P., Schlingensiepen, R., Schulmeyer, F. J., Jauch, T., Steinbrecher, A., Brawanski, A. T., Proescholdt, M. A., Schlaier, J. R., Buchroithner, J., et al. (2007) · Oligonucleotides · doi:10.1089/oli.2006.0053 · Cited by 215 · see citing works

TGF-β: the missing link in CD4+CD25+ regulatory T cell-mediated immunosuppression

Chen, W., & Wahl, S. M. (2003) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(03)00003-0 · Cited by 209 · see citing works

Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-β kinase antagonist, in mice

Bueno, L., de Alwis, D. P., Pitou, C., Yingling, J. M., Lahn, M., Glatt, S., & Trocóniz, I. F. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2007.10.008 · Cited by 204 · see citing works

Cyclin E and c‐Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins

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Targeted tumor therapy with the TGF-β2 antisense compound AP 12009

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Inhibition of the TGF-β receptor I kinase promotes hematopoiesis in MDS

Zhou, L., Nguyen, A. N., Sohal, D. P. S., Jing, Y., Pahanish, P., Gundabolu, K., Hayman, J., Chubak, A., Mo, Y., Bhagat, T. D., et al. (2008) · Blood · doi:10.1182/blood-2008-02-139824 · Cited by 185 · see citing works

Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesis

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Ki26894, a novel transforming growth factor‐β type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line

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Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis

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The MEK Pathway Is Required for Stimulation of p21WAF1/CIP1 by Transforming Growth Factor-β

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Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells

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Inhibition of Growth and Metastasis of Mouse Mammary Carcinoma by Selective Inhibitor of Transforming Growth Factor-β Type I Receptor Kinase In vivo

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Transforming growth factor beta type I receptor kinase mutant associated with metastatic breast cancer.

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Phase II trial of Belagenpumatucel-L, a TGF-β2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients

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Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft.

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