在晚期血液恶性肿瘤患者中进行 Akt 抑制剂三尖杉酯碱磷酸单水合物的 I 期临床、药代动力学和药效学研究。
Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.
机构信息
Departments of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX, USA.
出版信息
Leuk Res. 2013 Nov;37(11):1461-7. doi: 10.1016/j.leukres.2013.07.034. Epub 2013 Aug 6.
Abstract
Akt, a serine/threonine protein kinase, is constitutively phosphorylated and hyperactivated in multiple cancers, including acute myeloid leukemia. High levels are linked to poor survival and inferior responses to chemotherapy, making Akt inhibition an attractive therapeutic target. In this phase I/II study of TCN-PM, a small-molecule Akt inhibitor, TCN-PM therapy was well tolerated in patients with advanced hematological malignancies, and reduced levels of phosphorylation of Akt and its substrate Bad were shown, consistent with inhibition of this survival pathway and induction of cell death. Further investigation of TCN-PM alone or in combination in patients with high Akt levels is warranted.
摘要
Akt 是一种丝氨酸/苏氨酸蛋白激酶，在多种癌症中持续磷酸化和过度激活，包括急性髓性白血病。高水平与不良生存和对化疗反应不良相关，使得 Akt 抑制成为一个有吸引力的治疗靶点。在这项 TCN-PM（一种小分子 Akt 抑制剂）的 I/II 期研究中，TCN-PM 治疗在晚期血液恶性肿瘤患者中耐受性良好，并且显示 Akt 和其底物 Bad 的磷酸化水平降低，与该存活途径的抑制和细胞死亡的诱导一致。进一步研究 TCN-PM 单独或联合用于高 Akt 水平的患者是合理的。
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