Targeting the TGFβ pathway for cancer therapy.

By C. Neuzillet, Annemilaï Tijeras-Raballand, R. Cohen, J. Cros, S. Faivre, E. Raymond, A. de Gramont. Pharmacology and Therapeutics, 2015

609 citations recorded by the source corpus.

The TGFβ signaling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, motility and invasion, extracellular matrix production, angiogenesis, and immune response. TGFβ signaling deregulation is frequent in tumors and has crucial roles in tumor initiation, development and metastasis. TGFβ signaling inhibition is an emerging strategy for cancer therapy. The role of the TGFβ pathway as a tumor-promoter or suppressor at the cancer cell level is still a matter of debate, due to its differential effects at the early and late stages of carcinogenesis. In contrast, at the microenvironment level, the TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis. Then, targeting the TGFβ pathway in cancer may be considered primarily as a microenvironment-targeted strategy. In this review, we focus on the TGFβ pathway as a target for cancer therapy. In the first part, we provide a comprehensive overview of the roles played by this pathway and its deregulation in cancer, at the cancer cell and microenvironment levels. We go on to describe the preclinical and clinical results of pharmacological strategies to target the TGFβ pathway, with a highlight on the effects on tumor microenvironment. We then explore the perspectives to optimize TGFβ inhibition therapy in different tumor settings.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/6b03264319ea03274a2ad339cf6a797330452568

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In Molecular Biology

1. V. Plaks
2. Niwen Kong
3. Zena Werb
4. Pengfei Lu
5. M. Egeblad
6. Raghu Kalluri

In Oncology

1. V. Plaks
2. Zena Werb
3. Niwen Kong
4. A. Damjanović
5. M. Nedeljković
6. Pengfei Lu
7. M. Egeblad
8. Raghu Kalluri

Citations in the corpus

• Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge (2019, background): “In oncology, TGF-β signaling is known to promote EMT, proliferation, angiogenesis, metastatic spread, chemotherapy resistance, and has an immuno-modulating effect [53].”
• The Cancer Stem Cell Niche: How Essential is the Niche in Regulating Stemness of Tumor Cells? (2015, positive): “…1 (Snail), and Twist family basic helixloop-helix transcription factor (Twist) and increase the crosstalk with the TGF-b signaling pathway which stimulates self-renewal (Smith et al., 2012; Cabarcas et al., 2011); thus, they can induce EMT and ultimately promote migration and invasion of CSCs.”