Kahán Zsuzsanna
Általános Orvostudományi Kar, Szegedi Tudományegyetem, Onkoterápiás Klinika, Szeged.
Magy Onkol. 2020 Mar 17;64(1):13-24. Epub 2020 Feb 10.
Germinal or somatic mutations of the BRCA genes may serve as therapeutic targets. Deficient functioning of the BRCA genes render the cancer vulnerable to such therapeutic interventions as chemotherapy with DNA-targeted agents and PARP inhibitors targeting DNA repair capacity. Although BRCA mutations may be detected in a large variety of cancers, the mentioned specific therapies are efficient in the so called BRCA-associated cancers only including ovarian, breast, pancreatic, prostate cancers and the rare uterine sarcomas. While in ovarian and prostate carcinomas both germinal and somatic, in breast and pancreatic cancers exclusively germinal, and in uterine sarcomas mostly somatic mutations specify the tumor as BRCA-dependent; platinum-sensitivity in ovarian cancer may replace BRCA testing by indicating the presence of frequent DNA repair deficiency. Platinum-based chemotherapy is frequently efficient in BRCA-dependent cancers, while PARP inhibitors yet registered for ovarian, breast and pancreatic cancers bring paradigm change in the treatment of ovarian cancer and provide an additional treatment option of the others.
BRCA基因的生殖系或体细胞突变可能成为治疗靶点。BRCA基因功能缺陷使癌症易受针对DNA的化疗药物和靶向DNA修复能力的PARP抑制剂等治疗干预的影响。尽管在多种癌症中都可能检测到BRCA突变，但上述特定疗法仅在所谓的BRCA相关癌症中有效，这些癌症包括卵巢癌、乳腺癌、胰腺癌、前列腺癌和罕见的子宫肉瘤。在卵巢癌和前列腺癌中，生殖系和体细胞突变都有；在乳腺癌和胰腺癌中只有生殖系突变；在子宫肉瘤中大多是体细胞突变，这些突变将肿瘤确定为BRCA依赖型；卵巢癌中的铂敏感性可通过表明存在频繁的DNA修复缺陷来替代BRCA检测。铂类化疗在BRCA依赖型癌症中通常有效，而目前已获批用于卵巢癌、乳腺癌和胰腺癌的PARP抑制剂给卵巢癌治疗带来了范式转变，并为其他癌症提供了额外的治疗选择。
