伊德里希
医学
PI3K/AKT/mTOR通路
不利影响
淋巴瘤
临床试验
癌症研究
靶向治疗
肿瘤科
药理学
免疫学
内科学
癌症
伊布替尼
信号转导
慢性淋巴细胞白血病
白血病
生物
生物化学
作者
Vladimir Sapon-Cousineau,Sasha Sapon-Cousineau,Sarit Assouline
标识
DOI:10.1007/s11864-020-00746-8
摘要
Phosphatidylinositol 3-kinase (PI3K) inhibitors represent a novel class of agents targeting the key cellular regulatory PI3K/AKT/mTOR pathway involved in crucial functions such as cellular proliferation, cell cycle regulation, protein synthesis, and cell motility. This review starts with an overview of the PI3K pathway and the rationale for its targeting in lymphoma and potential on-target side effects of PI3K inhibition. With three agents now FDA approved for the treatment of relapsed and refractory (R/R) indolent non-Hodgkin lymphoma (iNHL), idelalisib, copanlisib, and duvelisib, we aim to review the pivotal trials leading to their approval as well as their clinical applications according to lymphoma subtypes. Important treatment-related adverse events are also reviewed and a perspective on the clinical role of these agents is provided, as well as some practical guidance on how to prevent, monitor, and manage potential adverse events in the clinic. PI3K inhibitors have an established role in the management of R/R iNHL, but their use and development are hampered by adverse events, particularly when used in combination with other anti-lymphoma therapies. Finally, this review highlights areas in need of more research in order to optimally use these agents in the care of patients with lymphoma.
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