2. Academic Validation
  3. Targeting the TGFβ pathway for cancer therapy

Targeting the TGFβ pathway for cancer therapy

  • Pharmacol Ther. 2015 Mar;147:22-31. doi: 10.1016/j.pharmthera.2014.11.001.
Cindy Neuzillet 1,  Annemilaï Tijeras-Raballand 2,  Romain Cohen 2,  Jérôme Cros 3,  Sandrine Faivre 1,  Eric Raymond 4,  Armand de Gramont 5
Affiliations

Affiliations

  • 1 INSERM U728 & U773 and Department of Medical Oncology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France.
  • 2 AAREC Filia Research, Translational Department, 1 place Paul Verlaine, 92100 Boulogne-Billancourt, France.
  • 3 Department of Pathology, Beaujon University Hospital (AP-HP - PRES Paris 7 Diderot), 100 boulevard du Général Leclerc, 92110 Clichy, France.
  • 4 New Drug Evaluation Laboratory, Centre of Experimental Therapeutics and Medical Oncology, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne, Switzerland.
  • 5 New Drug Evaluation Laboratory, Centre of Experimental Therapeutics and Medical Oncology, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne, Switzerland. Electronic address: armand.de-gramont@chuv.ch.
PMID: 25444759 DOI: 10.1016/j.pharmthera.2014.11.001
Abstract

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.

Keywords

Angiogenesis; Fibrosis; Metastasis; Microenvironment; TGFβ inhibitors; Tumor-stroma interactions.

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