Therapeutic targeting of TGF-β in lung cancer.

Sajjad Aftabi, Amir Barzegar Behrooz, Marco Cordani, Niloufar Rahiman, Mohammadamin Sadeghdoust, Farnaz Aligolighasemabadi, Stephen Pistorius, Seyedeh Hoda Alavizadeh, Nima Taefehshokr, Saeid Ghavami
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Abstract

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.

肺癌中 TGF-β 的治疗靶点。
转化生长因子-β(TGF-β)在肺癌的病理生理学中扮演着复杂的角色,最初作为肿瘤抑制因子抑制早期肿瘤的生长。但到了晚期,它的作用就发生了变化,它不是直接促进细胞增殖,而是通过增强上皮-间质转化(EMT)和创造有利的肿瘤微环境来促进肿瘤进展。虽然 EMT 通常与增强迁移和侵袭能力而非增殖本身有关,但 TGF-β 对这一过程的影响促进了肿瘤转移的复杂动态。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避和化疗抗药性中的作用,使肺癌治疗更加复杂。本综述对 TGF-β 参与肺癌治疗、对化疗耐药性的作用以及对免疫反应的调节等方面的最新研究成果进行了深入综述。尽管临床试验和针对 TGF-β 通路的新疗法的开发遇到了相当大的挑战,但这篇综述强调了继续深入研究 TGF-β 作用的必要性。深入了解这些作用可能会为肺癌带来新的靶向疗法。尽管 TGF-β 信号在肿瘤中的作用错综复杂,而且以前也遇到过挑战,但进一步的研究可能会产生创新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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