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PI3K inhibitors have emerged as promising therapeutic agents due to their critical role in various cellular processes, particularly in cancer, where the PI3K pathway is frequently dysregulated. This review explores the evolutionary path of PI3K inhibitors from laboratory discovery to clinical application. The journey begins with early laboratory investigations into PI3K signaling and inhibitor development, highlighting fundamental discoveries that laid the foundation for subsequent advancements. Optimization strategies, including medicinal chemistry approaches and structural modifications, are scrutinized for their contributions to enhancing inhibitor potency, selectivity, and pharmacokinetic properties. The translation from preclinical studies to clinical trials is examined, emphasizing pivotal trials that evaluated efficacy and safety profiles. Challenges encountered during clinical development are critically assessed. Finally, the review discusses ongoing research directions and prospects for PI3K inhibitors, underscoring these agents' continuous evolution and therapeutic potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Mechanical ventilation is an advanced life support treatment for patients with acute respiratory failure. While stabilizing respiratory function, it also acts as an injury factor to exacerbate or lead to lung injury, that is, ventilation-induced lung injury (VILI). There may be a more subtle form of damage to VILI known as "biotrauma". However, the mechanism of biotrauma in VILI is still unclear. This article intends to review the mechanism of biotrauma of VILI from the aspects of inflammatory response, oxidative stress and complement activation, in order to provide a new strategy for clinical prevention and treatment of biotrauma caused by VILI.