The transforming growth factor-beta (TGFβ) pathway is essential during embryo development and in maintaining normal homeostasis. During malignancy, the TGFβ pathway is co-opted by the tumor to increase fibrotic stroma, to promote epithelial to mesenchymal transition increasing metastasis and producing an immune-suppressed microenvironment which protects the tumor from recognition by the immune system. Compelling preclinical data demonstrate the therapeutic potential of blocking TGFβ function in cancer. However, the TGFβ pathway cannot be described as a driver of malignant disease. Two small molecule kinase inhibitors which block the serine-threonine kinase activity of TGFβRI on TGFβRII, a pan-TGFβ neutralizing antibody, a TGFβ trap, a TGFβ antisense agent, an antibody which stabilizes the latent complex of TGFβ and a fusion protein which neutralizes TGFβ and binds PD-L1 are in clinical development. The challenge is how to most effectively incorporate blocking TGFβ activity alone and in combination with other therapeutics to improve treatment outcome.

转化生长因子-β (TGFβ) 途径在胚胎发育和维持正常体内平衡过程中至关重要。在恶性肿瘤期间，肿瘤选择TGFβ途径来增加纤维化基质，促进上皮到间质的转变，增加转移并产生免疫抑制的微环境，保护肿瘤免受免疫系统的识别。令人信服的临床前数据证明了阻断 TGFβ 功能在癌症中的治疗潜力。然而，TGFβ途径不能被描述为恶性疾病的驱动因素。两种小分子激酶抑制剂，可阻断 TGFβRII 上 TGFβRI 的丝氨酸-苏氨酸激酶活性，一种泛 TGFβ 中和抗体，一种 TGFβ 陷阱，一种 TGFβ 反义剂，一种稳定 TGFβ 潜在复合物的抗体和一种中和 TGFβ 的融合蛋白并结合 PD-L1 正在临床开发中。面临的挑战是如何最有效地单独结合阻断 TGFβ 活性以及与其他疗法相结合以改善治疗结果。