Section of Experimental Haematology, Cancer Division, Faculty of Medicine, University of Glasgow, and Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, Glasgow, UK.
J Pathol. 2010 Mar;220(4):404-18. doi: 10.1002/path.2669.
The recent and rapid development of molecularly targeted therapy is best illustrated by advances in the management of haematological malignancy. In myeloid diseases we have seen dramatic improvements in the overall survival and quality of life for patients with chronic myeloid leukaemia treated with ABL and Src/ABL kinase inhibitors and we are poised to discover whether JAK2 inhibitors may offer similar benefit in myeloproliferative diseases. For acute myeloid leukaemia, the introduction of ATRA and myelotarg have had major impacts on the design of therapy regimens and many novel targeted agents, including farnesyl transferase, FLT3 and histone deacetylase inhibitors, are now in clinical trial. In lymphoid malignancies the highlight has been the introduction of rituximab, with significant improvements in the management of non-Hodgkin lymphoma and chronic lymphocytic leukaemia. The last 10 years has experienced a rapidly expanding interest and acceptance that leukaemic stem cells, including an improved ability to target them, may hold the key to improved response and reduced relapse rates across both myeloid and lymphoid disease. We now eagerly anticipate an era in which a wealth of preclinical discoveries are progressed to the clinic.
近年来，分子靶向治疗发展迅速，在血液系统恶性肿瘤的治疗中取得了显著进展。在髓系疾病中，我们已经看到接受 ABL 和Src/ABL 激酶抑制剂治疗的慢性髓性白血病患者的总生存率和生活质量得到了显著改善，我们正准备发现 JAK2 抑制剂是否可能为骨髓增殖性疾病带来类似的益处。对于急性髓系白血病，ATRA 和米托坦的引入对治疗方案的设计产生了重大影响，许多新型靶向药物，包括法尼基转移酶、FLT3 和组蛋白去乙酰化酶抑制剂，目前正在临床试验中。在淋巴系统恶性肿瘤中，重点是引入利妥昔单抗，显著改善了非霍奇金淋巴瘤和慢性淋巴细胞白血病的治疗效果。过去 10 年，人们越来越关注和接受白血病干细胞，包括改善靶向白血病干细胞的能力，可能是改善髓系和淋巴系统疾病反应率和降低复发率的关键。我们现在急切地期待着一个将大量临床前发现推进到临床应用的时代。
