PDF(Pubmed)
Abstract：
Glioblastoma multiforme (GBM) is characterized by a high mortality rate, high resistance to cytotoxic chemotherapy, and radiotherapy due to its highly aggressive nature. The pathophysiology of GBM is characterized by multifarious genetic abrasions that deactivate tumor suppressor genes, induce transforming genes, and over-secretion of pro-survival genes, resulting in oncogene sustainability. Synthetic lethality is a destructive process in which the episode of a single genetic consequence is tolerable for cell survival, while co-episodes of multiple genetic consequences lead to cell death. This targeted drug approach, centered on the genetic concept of synthetic lethality, is often selective for DNA repair-deficient GBM cells with restricted toxicity to normal tissues. DNA repair pathways are key modalities in the generation, treatment, and drug resistance of cancers, as DNA damage plays a dual role as a creator of oncogenic mutations and a facilitator of cytotoxic genomic instability. Although several research advances have been made in synthetic lethality modalities for GBM therapy, no review article has summarized these therapeutic modalities. Thus, this review focuses on the innovative advances in synthetic lethality modalities for GBM therapy.
摘要：
多形性胶质母细胞瘤（GBM）的特点是死亡率高，对细胞毒性化疗的高抗性，和放射治疗由于其高度侵略性的性质。GBM的病理生理学特征是多种遗传磨损，使肿瘤抑制基因失活，诱导转化基因，以及促生存基因的过度分泌，导致癌基因的可持续性。合成致死性是一个破坏性过程，其中单个遗传后果的发作对于细胞存活是可以容忍的，而多重遗传后果的共同发作导致细胞死亡。这种靶向药物的方法，以合成杀伤力的遗传概念为中心，通常对DNA修复缺陷的GBM细胞具有选择性，对正常组织具有有限的毒性。DNA修复途径是生成过程中的关键模式，治疗,和癌症的耐药性，DNA损伤作为致癌突变的创造者和细胞毒性基因组不稳定性的促进者发挥着双重作用。尽管在GBM治疗的合成致死方式方面已经取得了一些研究进展，没有一篇综述文章对这些治疗方式进行了总结.因此，这篇综述集中在GBM治疗的合成致死方式方面的创新性进展.
