Aftabi Sajjad, Barzegar Behrooz Amir, Cordani Marco, Rahiman Niloufar, Sadeghdoust Mohammadamin, Aligolighasemabadi Farnaz, Pistorius Stephen, Alavizadeh Seyedeh Hoda, Taefehshokr Nima, Ghavami Saeid
Department of Human Anatomy and Cell Science, University of Manitoba College of Medicine, Winnipeg, Canada.
Paul Albrechtsen Research Institute, CancerCare Manitoba, University of Manitoba, Winnipeg, Canada.
FEBS J. 2025 Apr;292(7):1520-1557. doi: 10.1111/febs.17234. Epub 2024 Jul 31.
Transforming growth factor-β (TGF-β) plays a complex role in lung cancer pathophysiology, initially acting as a tumor suppressor by inhibiting early-stage tumor growth. However, its role evolves in the advanced stages of the disease, where it contributes to tumor progression not by directly promoting cell proliferation but by enhancing epithelial-mesenchymal transition (EMT) and creating a conducive tumor microenvironment. While EMT is typically associated with enhanced migratory and invasive capabilities rather than proliferation per se, TGF-β's influence on this process facilitates the complex dynamics of tumor metastasis. Additionally, TGF-β impacts the tumor microenvironment by interacting with immune cells, a process influenced by genetic and epigenetic changes within tumor cells. This interaction highlights its role in immune evasion and chemoresistance, further complicating lung cancer therapy. This review provides a critical overview of recent findings on TGF-β's involvement in lung cancer, its contribution to chemoresistance, and its modulation of the immune response. Despite the considerable challenges encountered in clinical trials and the development of new treatments targeting the TGF-β pathway, this review highlights the necessity for continued, in-depth investigation into the roles of TGF-β. A deeper comprehension of these roles may lead to novel, targeted therapies for lung cancer. Despite the intricate behavior of TGF-β signaling in tumors and previous challenges, further research could yield innovative treatment strategies.
转化生长因子-β(TGF-β)在肺癌病理生理学中发挥着复杂的作用,最初通过抑制早期肿瘤生长而充当肿瘤抑制因子。然而,其作用在疾病晚期发生演变,在该阶段它并非通过直接促进细胞增殖,而是通过增强上皮-间质转化(EMT)和营造有利的肿瘤微环境来促进肿瘤进展。虽然EMT通常与增强的迁移和侵袭能力相关,而非增殖本身相关,但TGF-β对这一过程的影响促进了肿瘤转移的复杂动态变化。此外,TGF-β通过与免疫细胞相互作用影响肿瘤微环境,这一过程受肿瘤细胞内遗传和表观遗传变化的影响。这种相互作用突出了其在免疫逃逸和化疗耐药中的作用,使肺癌治疗更加复杂。本综述对TGF-β参与肺癌、其对化疗耐药的贡献以及对免疫反应的调节的最新研究结果进行了批判性概述。尽管在临床试验和开发针对TGF-β途径的新治疗方法方面遇到了巨大挑战,但本综述强调了持续深入研究TGF-β作用的必要性。对这些作用的更深入理解可能会带来针对肺癌的新型靶向治疗方法。尽管TGF-β信号在肿瘤中的行为复杂且此前面临挑战,但进一步研究可能会产生创新的治疗策略。