Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review

SIMPLE SUMMARY: While the importance of transforming growth factor β (TGFβ) in cancer development and progression has long been recognized, a successful therapy targeting this cytokine has not been developed yet. The difficulty in blocking the tumor-promoting activity of this factor while maintaining the tumor suppressor effects can compromise the expected outcomes. This systematic review summarizes and discusses the different strategies being tested to regulate TGFβ expression in cancer treatment, as well as their associated side effects. ABSTRACT: Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of this factor, or the deregulation of its signaling cascade, can lead to different pathologies, including cancer. A great variety of therapeutic strategies targeting TGFβ, or the members included in its signaling pathway, are currently being researched in cancer treatment. However, the dual role of TGFβ, as a tumor suppressor or a tumor-promoter, together with its crosstalk with other signaling pathways, has hampered the development of safe and effective treatments aimed at halting the cancer progression. This systematic literature review aims to provide insight into the different approaches available to regulate TGFβ and/or the molecules involved in its synthesis, activation, or signaling, as a cancer treatment. The therapeutic strategies most commonly investigated include antisense oligonucleotides, which prevent TGFβ synthesis, to molecules that block the interaction between TGFβ and its signaling receptors, together with inhibitors of the TGFβ signaling cascade-effectors. The effectiveness and possible complications of the different potential therapies available are also discussed.