Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland.
Department of Hematooncology, Copernicus Memorial Hospital, Lodz, Poland.
Expert Opin Drug Metab Toxicol. 2023 Sep;19(9):617-633. doi: 10.1080/17425255.2023.2260305. Epub 2023 Sep 15.
Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors are a class of novel agents that are mainly used to treat B-cell malignancies. They function by inhibiting one or more enzymes which are part of the PI3K/AKT/mTOR pathway. Idelalisib is a first-in-class PI3Kδ inhibitor effective in patients with B-cell lymphoid malignancies.
This article reviews the chemical structure, mechanism of action, and metabolic and toxicological properties of PI3Kδ inhibitors and discusses their clinical applications in monotherapy and in combination with other agents for the treatment of chronic lymphocytic leukemia (CLL). A search was conducted of PubMed, Web of Science, and Google Scholar for articles in English.
RESULTS/CONCLUSION: PI3Kδ inhibitors hold potential for the treatment of B-cell malignancies, including CLL. However, their use is also associated with severe toxicities, including pneumonia, cytopenias, hepatitis, and rash. Newer drugs are in development to reduce toxicity with novel schedules and/or combinations.
The development of novel PI3Kδ inhibitors might help to reduce toxicity and improve efficacy in patients with CLL and other B-cell lymphoid malignancies.
磷酸肌醇 3-激酶 δ（PI3Kδ）抑制剂是一类新型药物，主要用于治疗 B 细胞恶性肿瘤。它们通过抑制 PI3K/AKT/mTOR 通路的一个或多个酶来发挥作用。idelalisib 是一种首创的 PI3Kδ 抑制剂，对 B 细胞淋巴瘤恶性肿瘤患者有效。
本文综述了 PI3Kδ 抑制剂的化学结构、作用机制、代谢和毒理学特性，并讨论了其在单药治疗和与其他药物联合治疗慢性淋巴细胞白血病（CLL）方面的临床应用。检索了 PubMed、Web of Science 和 Google Scholar 上的英文文献。
结果/结论：PI3Kδ 抑制剂在治疗 B 细胞恶性肿瘤，包括 CLL 方面具有潜力。然而，它们的使用也与严重的毒性有关，包括肺炎、细胞减少症、肝炎和皮疹。正在开发新的药物，通过新的方案和/或联合用药来降低毒性。
新型 PI3Kδ 抑制剂的开发可能有助于降低 CLL 和其他 B 细胞淋巴瘤恶性肿瘤患者的毒性并提高疗效。
