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.

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http://dx.doi.org/10.1016/j.currproblcancer.2024.101172DOI Listing

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