TGFβ is a pleiotropic signaling pathway, which plays a pivotal role in regulating a multitude of cellular functions. TGFβ has a dual role in cell regulation where it induces growth inhibition and cell death; however, it can switch to a growth-promoting state under cancerous conditions. TGFβ is upregulated in CRC and pancreatic cancer, altering the tumor microenvironment, immune system, and promoting a mesenchymal state. The upregulation of TGFβ in certain cancers leads to resistance to immunotherapy, and attempts to inhibit TGFβ expression have led to reduced therapeutic resistance when combined with chemo- and immunotherapy. Here, we review the current TGFβ inhibitor drugs in clinical trials for pancreatic and colorectal cancer, with the goal of uncovering advances in improving clinical efficacy for TGFβ combinational treatments in patients. Furthermore, we discuss the relevance of alterations in TGFβ signaling and germline variants in the context of personalizing treatment for patients who show lack of response to current therapeutics.

中文翻译：

---

胰腺癌和结直肠癌中的 TGFβ：克服治疗耐药性的机会


TGFβ是一种多效性信号通路，在调节多种细胞功能中发挥着关键作用。 TGFβ 在细胞调节中具有双重作用，可诱导生长抑制和细胞死亡。然而，在癌症条件下它可以转变为促生长状态。 TGFβ 在结直肠癌和胰腺癌中表达上调，改变肿瘤微环境、免疫系统并促进间充质状态。某些癌症中 TGFβ 的上调会导致对免疫治疗的抵抗，而抑制 TGFβ 表达的尝试在与化疗和免疫治疗相结合时会导致治疗抵抗力降低。在此，我们回顾了目前在胰腺癌和结直肠癌临床试验中的 TGFβ 抑制剂药物，旨在揭示提高 TGFβ 联合治疗患者临床疗效的进展。此外，我们还讨论了 TGFβ 信号传导和种系变异的改变在对当前治疗缺乏反应的患者进行个性化治疗的背景下的相关性。