TGFβ belongs to a large family of widespread and evolutionarily conserved polypeptide growth factors that contributes to the orchestration and modulation of the developmental program, growth and differentiation profile and functional homeostasis of almost all cell types and tissues. Mutation or deletion of TGFβ signaling components is frequent in human cancer indicating a tumor suppressor role for this growth factor. However TGFβ has a dual role in cancer since TGFβ growth inhibitory responses in early stage cancer are replaced by invasive and pro-metastatic responses in advanced stages. These autocrine and paracrine pro-metastatic effects gave rise to the development of novel anti-cancer therapies. Several strategies have been developed to counteract the pro-metastatic activities of TGFβ: blocking the generation of TGFβ, blocking the interaction of TGFβ with its cognate receptors, and blocking the signaling cascade following receptor activation. These different approaches have yielded promising results and several molecules are currently in advanced clinical trials. Finally a novel class of small non-coding RNAs, the micro-RNAs, may represent interesting targets. Indeed, microRNAs are key regulators of biological processes and are involved in the development and progression of human diseases, particularly cancer. Thus, microRNA-based therapies could potentially modulate the pro-metastatic arm of TGFβ signaling specifically without affecting the tumor suppressor arm. In this review, we will describe the various existing strategies aiming at targeting TGFβ signaling in human cancer as well as potential novel approaches targeting microRNAs.
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