Szentmartoni Gyongyver, Mühl Dorottya, Csanda Renata, Szasz Attila Marcell, Herold Zoltan, Dank Magdolna
Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary.
Biomedicines. 2024 Mar 6;12(3):593. doi: 10.3390/biomedicines12030593.
Ten percent of patients with breast cancer, and probably somewhat more in patients with ovarian cancer, have inherited germline DNA mutations in the breast and ovarian cancer genes and . In the remaining cases, the disease is caused by acquired somatic genetic and epigenetic alterations. Targeted therapeutic agents, such as poly ADP-ribose polymerases (PARP) inhibitors (PARPi), have emerged in treating cancers associated with germline mutations since 2014. The first PARPi was FDA-approved initially for ovarian cancer patients with germline mutations. Deleterious variants in the genes and homologous recombination deficiency status have been strong predictors of response to PARPi in a few solid tumors since then. However, the relevance of somatic mutations is less clear. Somatic -mutated tumors might also respond to this new class of therapeutics. Although the related literature is often controversial, recently published case reports and/or randomized studies demonstrated the effectiveness of PARPi in treating patients with somatic mutations. The aim of this review is to summarize the predictive role of somatic mutations and to provide further assistance for clinicians with the identification of patients who could potentially benefit from PARPi.
10%的乳腺癌患者，卵巢癌患者的比例可能更高，其乳腺癌和卵巢癌相关基因存在遗传性种系DNA突变。在其余病例中，疾病是由获得性体细胞遗传和表观遗传改变引起的。自2014年以来，靶向治疗药物，如聚ADP核糖聚合酶（PARP）抑制剂（PARPi），已用于治疗与种系突变相关的癌症。首个PARPi最初被美国食品药品监督管理局（FDA）批准用于患有种系突变的卵巢癌患者。从那时起，相关基因中的有害变异和同源重组缺陷状态一直是一些实体瘤对PARPi反应的有力预测指标。然而，体细胞突变的相关性尚不清楚。体细胞BRCA1/2突变的肿瘤可能也对这类新型治疗药物有反应。尽管相关文献往往存在争议，但最近发表的病例报告和/或随机研究证明了PARPi在治疗体细胞BRCA1/2突变患者中的有效性。本综述的目的是总结体细胞BRCA1/2突变的预测作用，并为临床医生识别可能从PARPi中获益的患者提供进一步帮助。
