Targeting transforming growth factor- β signaling for enhanced cancer chemotherapy

During the past decades, drugs targeting transforming growth factor-β (TGFβ) signaling have received tremendous attention for late-stage cancer treatment since TGFβ signaling has been recognized as a prime driver for tumor progression and metastasis. Nonetheless, in healthy and pre-malignant tissues, TGFβ functions as a potent tumor suppressor. Furthermore, TGFβ signaling plays a key role in normal development and homeostasis by regulating cell proliferation, differentiation, migration, apoptosis, and immune evasion, and by suppressing tumor-associated inflammation. Therefore, targeting TGFβ signaling for cancer therapy is challenging. Recently, we and others showed that blocking TGFβ signaling increased chemotherapy efficacy, particularly for nanomedicines. In this review, we briefly introduce the TGFβ signaling pathway, and the multifaceted functions of TGFβ signaling in cancer, including regulating the tumor microenvironment (TME) and the behavior of cancer cells. We also summarize TGFβ targeting agents. Then, we highlight TGFβ inhibition strategies to restore the extracellular matrix (ECM), regulate the tumor vasculature, reverse epithelial-mesenchymal transition (EMT), and impair the stemness of cancer stem-like cells (CSCs) to enhance cancer chemotherapy efficacy. Finally, the current challenges and future opportunities in targeting TGFβ signaling for cancer therapy are discussed.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research