■患有复发性或进行性胶质母细胞瘤的患者很少对挽救疗法有反应。然而,全面的基因组分析可以提供洞察力,可以识别有前途的方法。信号通路分析揭示了合成致命的伙伴关系,这创造了靶向由肿瘤抑制基因丢失引起的脆弱性的可能性。对于正常组织中不存在的合成致命漏洞,可以在不引起正常组织毒性的情况下实现对癌细胞的致死性细胞毒性。该病例报告描述了一名患有进行性胶质母细胞瘤的患者,其染色体9p21纯合缺失。
■培美曲塞利用了CDKN2A和MTAP丢失造成的漏洞,贝伐单抗,和坎地沙坦通过靶向多个合成致死性淋巴结来实现有临床意义的缓解。
■合成杀伤力可以揭示异常反应的基础,从而扩大了分子谱分析的效用,实现了精准医学的承诺。
UNASSIGNED: Patients with relapsed or progressive glioblastoma only rarely respond to salvage therapies. Nevertheless, comprehensive genomic profiling can provide insight that can identify promising approaches. Signaling pathway analyses have revealed synthetic lethal partnerships, which create the possibility of targeting vulnerabilities arising from the loss of tumor suppressor genes. For synthetic lethal vulnerabilities that are not present in normal tissues, lethal cytotoxicity against cancer cells can be achieved without the necessity of causing normal tissue toxicity. This
case report describes a patient with progressive glioblastoma with homozygous deletion of chromosome 9p21.
UNASSIGNED: Vulnerabilities created by CDKN2A and MTAP loss were exploited with pemetrexed, bevacizumab, and candesartan to achieve a clinically meaningful remission by targeting multiple synthetic lethal nodes.
UNASSIGNED: Synthetic lethality can reveal the basis for exceptional responsiveness, thus extending the utility of molecular profiling and fulfilling the promise of precision medicine.