TGF‑β1 in cancer: From tumour suppressor to promoter, molecular mechanisms, and precision therapeutic strategies (Review)

Transforming growth factor‑β1 (TGF‑β1) plays a dual role in cancer progression, acting as both a tumour suppressor and a tumour promoter, with complex and stage‑dependent mechanisms of action. This article systematically reviews the molecular switching mechanism of TGF‑β1 from a tumour suppressor to a tumour promoter and its systemic regulatory network in the tumour microenvironment. In the process through which TGF‑β1 regulates cancer progression, its signalling pathways promote tumour invasion, metastasis and chemotherapy resistance through SMAD mutation, receptor expression downregulation, epithelial‑mesenchymal transition activation, immune escape, non‑SMAD pathway activation and remodelling of the tumour microenvironment. Although TGF‑β1‑targeting therapies such as antibodies, kinase inhibitors and antisense oligonucleotides face limitations in terms of efficacy and toxicity, combination immunotherapy (such as anti‑PD‑1 therapy) has the potential to enhance antitumour responses. Future precision intervention needs to integrate the dimension of time to distinguish between early tumour suppression and late tumour promotion windows, the dimension of spatiality and cell type to analyse the signal heterogeneity between primary and metastatic lesions, the dimension of signalling networks to selectively inhibit SMAD and non‑SMAD pathways, and the dimension of technology, such as using single‑cell sequencing and organoid models to guide personalised treatment, thereby achieving effective regulation of the complex role of TGF‑β1 in cancer progression.