11月8日，英国癌症研究所宣布，根据他们发表在美国最新一期学术刊物Cancer Cell上的研究论文"Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukaemia"，对于慢性髓性白血病中有些癌细胞对常用治疗药物出现耐药性的问题，他们发现了可以通过添加另一种药物来杀死这些癌细胞，从而保持治疗的有效性。
据介绍，慢性髓性白血病(chronic myeloid leukaemia, CML)是俗称“血癌”的白血病中较常见的一种，现在常用的治疗药物是伊马替尼和尼罗替尼，但是有些癌细胞已对它们产生了耐药性，药物不再能有效杀死这些癌细胞。
研究人员发现，一种名为MEK的蛋白质在这些癌细胞的生存中发挥着重要作用，使用能抑制这种蛋白质功能的药物有助于杀死癌细胞，如果联合使用MEK抑制剂和尼罗替尼，那些已产生耐药性的慢性髓性白血病癌细胞也可以被杀死。
参与研究的Richard Marais说，在慢性髓性白血病(chronic myeloid leukaemia, CML)的治疗中耐药性是个显著问题，本次研究为此找到了一种应对方法，接下来将通过人类临床试验测试这种方法的有效性。（生物谷Bioon.com）
doi:10.1016/j.ccr.2011.11.004
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Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukaemia
Leisl M. Packer, Sareena Rana, Robert Hayward, Thomas O'Hare, Christopher A. Eide, Ana Rebocho, Sonja Heidorn, Matthew S. Zabriskie, Ion Niculescu-Duvaz, Brian J. Druker, Caroline Springer, Richard Marais
We show that imatinib, nilotinib, and dasatinib possess weak off-target activity against RAF and, therefore, drive paradoxical activation of BRAF and CRAF in a RAS-dependent manner. Critically, because RAS is activated by BCR-ABL, in drug-resistant chronic myeloid leukemia (CML) cells, RAS activity persists in the presence of these drugs, driving paradoxical activation of BRAF, CRAF, MEK, and ERK, and leading to an unexpected dependency on the pathway. Consequently, nilotinib synergizes with MEK inhibitors to kill drug-resistant CML cells and block tumor growth in mice. Thus, we show that imatinib, nilotinib, and dasatinib drive paradoxical RAF/MEK/ERK pathway activation and have uncovered a synthetic lethal interaction that can be used to kill drug-resistant CML cells in vitro and in vivo.
