Department of Medical Oncology, Dana-Farber Cancer Institute, M551, 450 Brookline Avenue, Boston, MA 02115, USA.
Curr Cancer Drug Targets. 2013 Sep;13(7):711-23. doi: 10.2174/15680096113139990085.
Over the past decades the prognosis of patients with Chronic Myeloid Leukemia (CML) has radically changed due to groundbreaking scientific and translational studies that have revealed the biologic basis of such a hematologic malignancy. These studies have led to the rapid development of many BCR-ABL specific tyrosine kinase inhibitors (TKIs), such as Imatinib, Nilotinib and Dasatinib, which have improved 10-years survival to more than 80%. Although these therapies represent a landmark step in the race for the cure of CML, they did not change the progression in advanced phase of disease. Therefore unravel the molecular mechanisms and the biological basis of CML, especially during the advanced stage, is of seminal importance as this would result in the design of more effective and less toxic therapies. In such a scenario, several novel drugs designed to specifically target biological features of CML cells are currently in clinical trials with promising results that would provide not only improve the therapeutic armamentarium but also to overcome drug resistance of this tumor. Here we review recent advances in biology of CML and their therapeutic implications.
在过去的几十年中,由于开创性的科学和转化研究揭示了这种血液系统恶性肿瘤的生物学基础,慢性髓性白血病(CML)患者的预后发生了根本性变化。这些研究导致了许多 BCR-ABL 特异性酪氨酸激酶抑制剂(TKI)的快速发展,如伊马替尼、尼罗替尼和达沙替尼,它们将 10 年生存率提高到了 80%以上。尽管这些治疗方法代表了治愈 CML 的竞赛中的一个里程碑式的步骤,但它们并没有改变疾病晚期的进展。因此,揭示 CML 的分子机制和生物学基础,特别是在晚期阶段,具有重要意义,因为这将导致设计更有效和毒性更小的治疗方法。在这种情况下,目前有几种专门针对 CML 细胞生物学特征的新型药物正在临床试验中,结果令人鼓舞,不仅将改善治疗手段,还将克服这种肿瘤的耐药性。在这里,我们回顾了 CML 生物学的最新进展及其治疗意义。