众所周知，磷脂酰肌醇 3 激酶 (PI3K) 家族包含三类细胞内酶。 I 类 PI3K 主要通过响应细胞表面受体刺激而发挥信号传导作用，而 II 类和 III 类更多地参与膜转运。在正常生理条件下，PI3K信号网络协调细胞生长、分裂、迁移和存活。 PI3K 信号通路的异常激活会破坏细胞活动和新陈代谢，通常标志着癌症的发生。目前，美国食品药品监督管理局（FDA）已批准5种I类PI3K抑制剂的临床使用。这些小分子抑制剂对不同的 I 类 PI3K 家族成员表现出不同的选择性，主要用于治疗乳腺癌和血液恶性肿瘤。因此，开发新型I类PI3K抑制剂一直是肿瘤学领域的一个重要研究热点，旨在提高潜在的治疗选择性和有效性。在这篇综述中，我们总结了 PI3K 的具体结构及其在癌症进展中的功能作用。此外，我们严格评估针对 I 类 PI3K 的小分子抑制剂，特别关注其在癌症治疗中的临床应用。此外，我们的目标是分析以异常 PI3K 激活为标志的不同类型癌症的治疗方法，并确定适合小分子抑制剂干预的潜在分子靶点。最终，我们提出了开发治疗策略的未来方向，通过调节 PI3K 家族来优化癌症治疗结果。© 2024。作者。

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family.© 2024. The Author(s).