Stanford University Cancer Center, Stanford, CA; and.
Stanford Cancer Institute, Stanford, CA.
Blood Adv. 2018 Oct 23;2(20):2787-2797. doi: 10.1182/bloodadvances.2018015834.
The clinical heterogeneity of the myelodysplastic syndromes (MDSs) relates to the recently discerned panoply of molecular abnormalities extant within this disease spectrum. Despite increasing recognition of these biologic abnormalities, very limited therapeutic options exist to exploit our increasing understanding of the molecular pathophysiology of MDS, with only 1 therapy (lenalidomide) particularly focused on a specific clinical patient subset (del(5q) cytogenetics) and 2 epigenetic modulators (azacitidine and decitabine) having been approved for treating these patients. This article will review the mutational and biologic landscape of these disorders, as well as the targeted therapeutics currently in clinical trials that are focused on attacking these features. Given the molecular complexity of these disorders and the limited repertoire of effective therapeutic agents, we will also discuss novel approaches attempting to determine potentially effective and personalized treatment options through complementary chemosensitivity and computerized signaling network screening for these disparate MDS patient subsets. Translational use of such resources, combined with the rapidly evolving next-generation molecular technologies, should prove useful in effectuating improved and more selective options for therapy.
骨髓增生异常综合征（MDS）的临床异质性与该疾病谱中最近发现的各种分子异常有关。尽管人们越来越认识到这些生物学异常，但可利用我们对 MDS 分子病理生理学日益增长的理解的治疗方法非常有限，只有 1 种治疗方法（来那度胺）特别针对特定的临床患者亚组（del(5q) 细胞遗传学），并且只有 2 种表观遗传调节剂（阿扎胞苷和地西他滨）被批准用于治疗这些患者。本文将回顾这些疾病的突变和生物学特征，以及目前正在临床试验中针对这些特征的靶向治疗药物。鉴于这些疾病的分子复杂性和有效治疗药物的有限组合，我们还将讨论通过对这些不同的 MDS 患者亚组进行互补的化疗敏感性和计算机信号网络筛选，尝试确定潜在有效和个性化治疗方案的新方法。此类资源的转化应用，结合快速发展的下一代分子技术，应有助于为治疗提供更好和更有针对性的选择。
