简介:急性髓系白血病(AML)是一种临床异质性血液系统恶性肿瘤,长期预后较差。细胞毒性化疗仍然是治疗的支柱,尤其是在年轻患者中;然而,有效结合靶向治疗仍然是积极研究的领域,以努力改善反应持续时间和生存率。细胞周期抑制剂(CCI)是一类新的药剂,其对于AML患者的发展可能是特别感兴趣的。涵盖的领域:我们将回顾CCI的概念以及北美和国外AML治疗的临床前和临床数据。具体的药物靶点包括细胞周期蛋白D激酶,极光激酶,CHK1和WEE1。专家意见:在AML患者中使用CCI是一种新兴的方法,已在临床前模型中显示出希望。到目前为止,将这一概念转化为临床成功一直具有挑战性,由于边际单一药物活性和显著的毒性,然而,临床评估仍在进行中.将这些药剂添加到细胞毒性化疗和其他靶向疗法中,为这类新型疗法提供了潜在的组合途径。在平衡毒性的同时开发最佳组合是我们可以预期将这些药物用于AML治疗的医疗设备之前必须克服的首要临床挑战之一。
Introduction: Acute myeloid leukemia (AML) is a clinically heterogeneous hematologic malignancy with poor long term outcomes. Cytotoxic chemotherapy remains the backbone of therapy especially among younger patients; however the effective incorporation of targeted therapies continues to be an area of active research in an effort to improve response durations and survival. Cell cycle inhibitors (CCI) are a novel class of agents which may be of particular interest for development in patients with AML. Areas covered: We will
review the concept of CCIs along with available pre-clinical and clinical data in the treatment of AML both in North America and abroad. Specific drug targets reviewed include cyclin D kinase, Aurora kinase,
CHK1, and WEE1. Expert opinion: Utilization of CCIs in patients with AML is an emerging approach that has shown promise in pre-clinical models. It has been challenging to translate this concept into clinical success thus far, due to marginal single-agent activity and significant toxicity profiles, however clinical evaluation is ongoing. Addition of these agents to cytotoxic chemotherapy and other targeted therapies provides a potential combinatorial path forward for this novel class of therapies. Developing optimal combinations while balancing toxicity are among the top clinical challenges that must be overcome before we can anticipate adoption of these agents into the armamentarium of AML therapy.