磷脂酰肌醇3-激酶（PI3K）信号通路调节细胞存活、增殖、迁移、代谢及其他关键细胞生命过程。此外，PI3K信号通路的激活对癌症发展至关重要。因此，已经开发了多种PI3K 抑制剂进行肿瘤治疗。虽然几种PI3K抑制剂已经获得了美国食品和药物管理局（FDA）批准用于抗肿瘤活性显著的治疗，但频繁和严重的不良反应极大地限制了它们的临床应用。这些毒性通常是靶向和免疫介导的，但其潜在机制仍不清楚。目前的处理通常涉及对症治疗的干预，如症状持续则停药。因此，有必要全面了解这些不良事件，并通过建立最有效的管理指南、适当的间歇用药方案和新的组合用药来确保PI3K抑制剂的临床安全应用。本文聚焦于PI3K抑制剂在癌症治疗中的发展，特别是对特异性亚型的PI3K抑制剂的强调。同时，也涵盖了PI3K抑制剂最常见的不良反应、潜在机制和处理方法。© 2023. The Author(s).

The phosphatidylinositol 3-kinase (PI3K) signalling pathway regulates cell survival, proliferation, migration, metabolism and other vital cellular life processes. In addition, activation of the PI3K signalling pathway is important for cancer development. As a result, a variety of PI3K inhibitors have been clinically developed to treat malignancies. Although several PI3K inhibitors have received approval from the Food and Drug Administration (FDA) for significant antitumour activity, frequent and severe adverse effects have greatly limited their clinical application. These toxicities are mostly on-target and immune-mediated; nevertheless, the underlying mechanisms are still unclear. Current management usually involves intervention through symptomatic treatment, with discontinuation if toxicity persists. Therefore, it is necessary to comprehensively understand these adverse events and ensure the clinical safety application of PI3K inhibitors by establishing the most effective management guidelines, appropriate intermittent dosing regimens and new combination administration. Here, the focus is on the development of PI3K inhibitors in cancer therapy, with particular emphasis on isoform-specific PI3K inhibitors. The most common adverse effects of PI3K inhibitors are also covered, as well as potential mechanisms and management approaches.© 2023. The Author(s).