Department of Medical Biology and Pathology, Gustave Roussy, Cancer Genetics Laboratory, Gustave Roussy, 94800 Villejuif, France.
Department of Clinical Oncology, A.C. Camargo Cancer Center, São Paulo 01509-010, Brazil.
Int J Mol Sci. 2020 May 28;21(11):3850. doi: 10.3390/ijms21113850.
Ovarian and breast cancers are currently defined by the main pathways involved in the tumorigenesis. The majority are carcinomas, originating from epithelial cells that are in constant division and subjected to cyclical variations of the estrogen stimulus during the female hormonal cycle, therefore being vulnerable to DNA damage. A portion of breast and ovarian carcinomas arises in the context of DNA repair defects, in which genetic instability is the backdrop for cancer initiation and progression. For these tumors, DNA repair deficiency is now increasingly recognized as a target for therapeutics. In hereditary breast/ovarian cancers (HBOC), tumors with mutations present an impairment of DNA repair by homologous recombination (HR). For many years, mutations were only screened on germline DNA, but now they are also searched at the tumor level to personalize treatment. The reason of the inactivation of this pathway remains uncertain for most cases, even in the presence of a HR-deficient signature. Evidence indicates that identifying the mechanism of HR inactivation should improve both genetic counseling and therapeutic response, since they can be useful as new biomarkers of response.
卵巢癌和乳腺癌目前是通过肿瘤发生过程中的主要途径来定义的。大多数癌症是癌，起源于上皮细胞，上皮细胞不断分裂，并在女性荷尔蒙周期中受到雌激素刺激的周期性变化，因此容易受到 DNA 损伤。一部分乳腺癌和卵巢癌发生在 DNA 修复缺陷的情况下，其中遗传不稳定性是癌症发生和进展的背景。对于这些肿瘤，DNA 修复缺陷现在越来越被认为是治疗的靶点。在遗传性乳腺癌/卵巢癌 (HBOC) 中，存在 突变的肿瘤表现出同源重组 (HR) 的 DNA 修复受损。多年来， 突变仅在种系 DNA 上进行筛查，但现在也在肿瘤水平上进行筛查，以实现个体化治疗。即使存在 HR 缺陷特征，大多数情况下这种途径失活的原因仍不确定。有证据表明，确定 HR 失活的机制应该可以改善遗传咨询和治疗反应，因为它们可以作为新的反应生物标志物。
