Breccia Massimo, Molica Matteo, Alimena Giuliana
Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
Leuk Res. 2014 Dec;38(12):1392-8. doi: 10.1016/j.leukres.2014.09.016. Epub 2014 Oct 5.
Tyrosine kinase inhibitors (TKIs) advent has deeply changed the outcome of chronic myeloid leukemia (CML) patients, with improved rates of response and overall survival. However, for this success some patients paid the price of a number of peculiar side effects, the so-called off-target side effects, specific for each one TKI. These effects are due to non-selective inhibition of other tyrosine kinase receptors, such as PDGFR, c-KIT, Src, VEGF. Consequences of this inhibition, some metabolic changes during the treatment with TKIs are reported. Aim of present review is to report metabolic changes and potential mechanisms involved in the pathogenesis related to imatinib, second (nilotinib and dasatinib) and third generation (bosutinib and ponatinib) TKIs.
酪氨酸激酶抑制剂(TKIs)的出现深刻改变了慢性髓性白血病(CML)患者的治疗结局,缓解率和总生存率均有所提高。然而,为了这一成功,一些患者付出了代价,出现了许多特定的副作用,即所谓的脱靶副作用,每种TKI都有其特异性。这些效应是由于对其他酪氨酸激酶受体(如PDGFR、c-KIT、Src、VEGF)的非选择性抑制所致。据报道,这种抑制的后果是在使用TKIs治疗期间出现了一些代谢变化。本综述的目的是报告与伊马替尼、第二代(尼罗替尼和达沙替尼)和第三代(博舒替尼和波纳替尼)TKIs相关的代谢变化及其发病机制中的潜在机制。