PI3Kδ抑制剂在B细胞淋巴瘤中的应用情况

Application Situation on PI3Kδ Inhibitors in B-cell Lymphoma

关键词:  PI3Kδ抑制剂  B细胞淋巴瘤  联合用药  不良反应

Key words:  PI3Kδ inhibitor  B-cell lymphoma  drug combination  adverse reactions

摘要:

PI3K/AKT/mTOR信号通路在细胞的增殖、存活、分化、运动和胞内运输等生物功能中发挥了至关重要的作用。PI3Kδ作为PI3K的一个亚型，在B淋巴细胞中高表达并参与了B细胞淋巴瘤的恶性进展。因此，开发以PI3Kδ为靶点的抑制剂已成为抗B细胞淋巴瘤研究领域的热点。目前，已有多种PI3Kδ抑制剂被FDA批准用于B细胞淋巴瘤的治疗，其各具特点，但在临床上也存在着不同程度的不良反应。由于B细胞淋巴瘤发病机制的复杂性及多样性，单靶点的PI3Kδ抑制剂疗效往往有限，且易产生耐药性，常需联合化疗或其他靶向药物以提升疗效。PI3Kδ抑制剂的未来发展趋势是开发高效低毒的新型抑制剂，或者探索与化疗、放疗及靶向药物等联合运用以达到更好的抗肿瘤效果同时减少不良反应的治疗方案。本文针对已上市和尚处于临床研究阶段的PI3Kδ抑制剂进行综述，重点围绕其作用特点、不良反应及联合用药方案。

Abstract:

PI3K/AKT/mTOR signaling pathway plays a crucial role in cell proliferation, survival, differentiation, motility and intracellular transport. PI3Kδ, an isoform of PI3K, is highly expressed in B lymphocytes and is involved in the malignant progression of B-cell lymphoma. Thus, PI3Kδ has emerged as an attractive target for the development of anti-B-cell lymphoma drugs. Currently, there are several PI3Kδ inhibitors approved by the FDA for the treatment of B-cell lymphoma, each with its own characteristics, but also with varying degrees of adverse effects in clinical practice. Due to the complexity and diversity of the pathogenesis of B-cell lymphoma, single-target PI3Kδ inhibitors often have limited efficacy and are prone to drug resistance, and need to be combined with chemotherapy or other targeted drugs to enhance their efficacy. The future trend is to design novel inhibitors with higher efficacy and lower toxicity or to develop novel combination regimens with other chemotherapy, radiotherapy, and target drugs to acquire better anti-tumor effects with reduced adverse effects. This review summarizes the PI3Kδ inhibitors that have been approved for the treatment of B-cell lymphoma or are still in clinical trials, mainly focusing on their characteristics, adverse effects and combination regimens.