Mahajan Atharva, Panzade Gauri, Bhuniya Tiyasa, Das Purbasha, Bhattacharjee Bidyabati, Das Sagnik, Chowdhury Ankita, Chakraborty Kashmira, Guha Sudeepta, Samant Anushka, Dey Anuvab, Ghosh Subhrojyoti
Advance Centre for Treatment, Research and Education in Cancer (ACTREC), Navi Mumbai, Mumbai, Maharashtra, India.
Department of Biotechnology, National Institute of Technology Durgapur, West Bengal, India.
Curr Probl Cancer. 2025 Feb;54:101172. doi: 10.1016/j.currproblcancer.2024.101172. Epub 2024 Dec 27.
This comprehensive review explores the transformative potential of PROTAC (Proteolysis-Targeting Chimeras) therapy as a groundbreaking approach in the landscape of lung cancer treatment. The introduction provides a succinct overview of current challenges in lung cancer treatment, emphasizing the significance of targeted therapies. Focusing on PROTAC therapy, the article elucidates its mechanism of action, comparing it with traditional targeted therapies and highlighting the key components and design principles of PROTAC molecules. In the context of lung cancer, the review meticulously summarizes preclinical evidence, emphasizing efficacy and specificity gleaned from studies evaluating PROTAC therapy. It delves into the implications of this preclinical data, discussing potential advantages over existing targeted therapies. An update on ongoing clinical trials involving PROTAC therapy for lung cancer offers a snapshot of the current progress, with a summary of key outcomes and advancements in early-phase trials. The mechanistic insights into PROTAC therapy's impact on lung cancer cells are explored, alongside a discussion on potential biomarkers for patient stratification and response prediction. The influence of tumor heterogeneity on PROTAC therapy outcomes is also addressed. Safety and tolerability assessments, encompassing preclinical and clinical studies, are comprehensively evaluated, including a comparative analysis with traditional targeted therapies and strategies to mitigate side effects. Looking forward, the article discusses the future perspectives of PROTAC therapy in lung cancer treatment and addresses ongoing challenges, providing a nuanced exploration of potential combination therapies and synergistic approaches. In conclusion, the review summarizes key findings and insights, underscoring the tremendous potential of PROTAC therapy as a promising and innovative avenue in pursuing more effective lung cancer treatments.
本综述探讨了蛋白水解靶向嵌合体(PROTAC)疗法在肺癌治疗领域作为一种开创性方法的变革潜力。引言简要概述了肺癌治疗中的当前挑战,强调了靶向治疗的重要性。文章聚焦于PROTAC疗法,阐明了其作用机制,将其与传统靶向治疗进行比较,并突出了PROTAC分子的关键组成部分和设计原则。在肺癌背景下,该综述精心总结了临床前证据,强调了从评估PROTAC疗法的研究中获得的疗效和特异性。深入探讨了这些临床前数据的意义,讨论了与现有靶向治疗相比的潜在优势。关于肺癌PROTAC疗法正在进行的临床试验的最新情况提供了当前进展的概况,总结了早期试验的关键结果和进展。探讨了PROTAC疗法对肺癌细胞影响的机制见解,同时讨论了用于患者分层和反应预测的潜在生物标志物。还讨论了肿瘤异质性对PROTAC疗法结果的影响。全面评估了包括临床前和临床研究在内的安全性和耐受性评估,包括与传统靶向治疗的比较分析以及减轻副作用的策略。展望未来,文章讨论了PROTAC疗法在肺癌治疗中的未来前景,并解决了当前的挑战,对潜在的联合疗法和协同方法进行了细致入微的探索。总之,该综述总结了关键发现和见解,强调了PROTAC疗法作为追求更有效肺癌治疗的一种有前景的创新途径的巨大潜力。