Journal ArticleDOI
TGF-β signalling-related markers in cancer patients with bone metastasis
José Baselga,Mace L. Rothenberg,Josep Tabernero,Joan Seoane,Thomas Daly,Ann Cleverly,Brandi Berry,Susanne Kloeker Rhoades,Chad Ray,Jeffrey Fill,Daphne L. Farrington,Lisa Anne Wallace,Jonathan M. Yingling,Michael Lahn,Carlos L. Arteaga,Michael A. Carducci +15 more
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TLDR
This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-β inhibitor, and was positively correlated with increased platelet factor 4 levels, parathyroid-related protein, von Willebrand Factor and interleukin levels.Citations
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Targeting the TGFβ signalling pathway in disease.
Rosemary J. Akhurst,Akiko Hata +1 more
TL;DR: Why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGF β inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled using personalized approaches to dosing, monitoring of biomarkers as well as brief and/or localized drug-dosing regimens are considered.
Journal ArticleDOI
The PTEN–PI3K pathway: of feedbacks and cross-talks
TL;DR: The current status of the PTEN– PI3K signaling pathway is reviewed with special emphasis on the most recent data on targets and regulation of thePTEN–PI3K axis, which provides novel provocative therapeutic implications based on the targeted modulation of PI3k-cross-talking signals.
Journal ArticleDOI
Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway
Stephan Herbertz,J. Scott Sawyer,Anja Stauber,Ivelina Gueorguieva,Kyla Driscoll,Shawn T. Estrem,Ann Cleverly,Durisala Desaiah,Susan C. Guba,Karim A. Benhadji,Christopher A. Slapak,Michael Lahn +11 more
TL;DR: The use of a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib, and the past and current experiences with different pharmacological treatments that enabled it to be investigated in patients are summarized.
Targeting the TGFβ signalling pathway in disease
TL;DR: Why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGF β inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled using personalized approaches to dosing, monitoring of biomarkers as well as brief and/or localized drug-dosing regimens are considered.
Journal ArticleDOI
Transforming growth factor-β signaling: emerging stem cell target in metastatic breast cancer?
TL;DR: This model predicts that inhibiting TGFβ signaling should drive the differentiation of mammary stem cells into ductal cells, and proposes a novel anti-metastatic therapeutic approach that converts basal-like or HER2-positive cancers to a more epithelioid, non-proliferating phenotype.
References
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Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
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A multigenic program mediating breast cancer metastasis to bone.
Yibin Kang,Peter M. Siegel,Weiping Shu,Maria Drobnjak,Sanna M. Kakonen,Carlos Cordon-Cardo,Theresa A. Guise,Theresa A. Guise,Joan Massagué +8 more
TL;DR: Overexpression of this bone metastasis gene set is superimposed on a poor-prognosis gene expression signature already present in the parental breast cancer population, suggesting that metastasis requires a set of functions beyond those underlying the emergence of the primary tumor.
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Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
Peter M. Siegel,Joan Massagué +1 more
TL;DR: The cytostatic and apoptotic functions of transforming growth factor-β (TGF-β) help restrain the growth of mammalian tissues; loss of these effects leads to hyperproliferative disorders and is common in cancer.
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Autocrine growth factors and cancer.
TL;DR: The ability of cancer cells to produce and to respond to their own growth factors (autocrine secretion) has become a central concept linking oncogene and growth factor research.
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TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development
Juan Juan Yin,Katri Selander,John M. Chirgwin,Mark Dallas,Barry Grubbs,Rotraud Wieser,Joan Massagué,Gregory R. Mundy,Theresa A. Guise +8 more
TL;DR: An important role is demonstrated in the development of breast cancer metastasis to bone, via the TGF-beta receptor-mediated signaling pathway in tumor cells, and it is suggested that the bone destruction is mediated by PTHrP.