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Seong -Jin Kim is currently working as a professor at the PrecisionMedicine Research Center at the Advanced Institute of Convergence Technology, Seoul National University, Korea.
TGF-? is a multifunctional cytokine involved in diverse cellular functions, including cell growthandimmune responses.TGF-? signaling has emerged as a key architect of themicroenvironmentin poor-prognosis cancers. Disseminatedtumorcells show a strong dependency on aTGF-?-activated stroma during the establishment and subsequent expansion of metastasis.TGF-? also has a positive role on the cancer stem cell (CSC) population promoting or sustaining stemness of the pool of CSCs in diverse types of malignancy.Since TGF-? signaling is dysregulatedin most of humancancers, thus affecting the overall progression to malignancy, TGF-? signaling has been considered a potentially novel therapeutic targetfor treating resistance acquired by EMT.In the TGF-? signaling pathway, TGF-? receptor I kinase inhibitors have shown promise in blocking the TGF-?-mediated tumor progression and metastasis, and enhancing antitumor immunity in nonclinical animal models.Vactosertib, a TGF-? receptor I kinase inhibitor, has shown significant preclinical antitumor efficacy in a range of in vivo metastatic and orthotopic xenograft models and has completed phase 1 clinical trials in USA. Recent molecular classification of gastrointestinal cancer has identified a poor-prognosis transcriptional subtype associated with mesenchymal traits and genes upregulated by TGF-? in stromal cells are robust predictorsof cancer recurrence and metastasis. This observation warrants the development of anti-TGF-? therapies for the treatment of poor-prognosis cancers with TGF-?response signature.