Imyanitov E N
Vopr Onkol. 2016;62(2):221-6.
Until recently the detection of carriers of mutations in hereditary cancer genes was aimed almost exclusively to the detection of subjects-at-risk, and consequently, personalized monitoring and preventive actions. However, it was revealed several years ago that some hereditary cancers are characterized by unique biological features and, therefore, unusual spectrum of drug sensitivity. For example, BRCA1/2-associated cancers usually demonstrate somatic loss of the remaining gene allele, and, hence, tumor-specific defects of DNA repair of double-strand breaks. This mechanism determines increased sensitivity of BRCA1/2-related cancers to cisplatin, mitomycin C and PARP inhibitors. Cancers arising as a part of Lynch syndrome can be effectively treated by the modulators of immune response. Tumors in patients with tuberous sclerosis often regress after administration of mTOR inhibitors. For the time being, there is already about a dozen of drugs demonstrating specific activity towards certain categories of hereditary cancers.
直到最近,遗传性癌症基因中突变携带者的检测几乎完全旨在检测高危个体,从而进行个性化监测和预防措施。然而,几年前发现一些遗传性癌症具有独特的生物学特征,因此具有不同寻常的药物敏感性谱。例如,BRCA1/2相关癌症通常表现出剩余基因等位基因的体细胞缺失,因此存在双链断裂DNA修复的肿瘤特异性缺陷。这种机制决定了BRCA1/2相关癌症对顺铂、丝裂霉素C和PARP抑制剂的敏感性增加。作为林奇综合征一部分出现的癌症可以通过免疫反应调节剂有效治疗。结节性硬化症患者的肿瘤在使用mTOR抑制剂后通常会消退。目前,已经有大约十几种药物对某些类型的遗传性癌症表现出特定活性。