TGF-beta Signaling and Resistance to Cancer Therapy

The transforming growth factor beta (TGF-beta) pathway, which is well studied for its ability to inhibit cell proliferation in early stages of tumorigenesis while promoting epithelial-mesenchymal transition and invasion in advanced cancer, is considered to act as a double-edged sword in cancer. Multiple inhibitors have been developed to target TGF-beta signaling, but results from clinical trials were inconsistent, suggesting that the functions of TGF-beta in human cancers are not yet fully explored. Multiple drug resistance is a major challenge in cancer therapy; emerging evidence indicates that TGF-beta signaling may be a key factor in cancer resistance to chemotherapy, targeted therapy and immunotherapy. Finally, combining anti-TGF-beta therapy with other cancer therapy is an attractive venue to be explored for the treatment of therapy-resistant cancer.