依布替尼的临床应用及相关不良反应研究进展

Recent advances in clinical application of Ibrutinib and its related adverse events

依布替尼(Ibrutinib)是一种小分子激酶抑制剂,通过共价结合的方式选择性、不可逆性地抑制布鲁顿酪氨酸激酶(bruton tyrosine kinase,BTK)和白细胞介素-2诱导型T细胞激酶(interleukin-2-inducible T-cell kinase,ITK)的活性,损害B细胞和T细胞的功能。BTK是表达于多种造血细胞、B细胞淋巴瘤和白血病细胞的B细胞受体(B cell receptor,BCR)信号激酶[1]。

Ibrutinib is an orally administered covalent inhibitor of Bruton tyrosine kinase(BTK)that induces apoptosis of B cells.BTK is a member of the Tec family of non-receptor tyrosine kinases and has a well-established function in B-cell receptor(BCR)signaling pathway which plays an important role in the proliferation,survival,migration,and homing of normal and malignant B cells.Interleukin-2-inducible T-cell kinase(ITK)is a T-cell-dominant member of the Tec-kinase family that drives proximal T-cell receptor(TCR)signaling.Ibrutinib irreversibly binds ITK and inhibits activation of Th2 cells.Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an irreversible immunomodulatory inhibitor of both ITK and BTK.Common adverse events of ibrutinib are diarrhea,nausea,fatigue,rash,dyspnea.Whereas,adverse events like infections,atrial fibrillation,bleeding,hematologic toxicity,arthralgia and second primary malignancies may lead to treatment discontinuation,and worse still induce poor prognosis.