U.O.C Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy.
Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
Int J Mol Sci. 2019 Jul 10;20(14):3390. doi: 10.3390/ijms20143390.
Breast cancer (BC) is the most frequent oncologic cause of death among women and the improvement of its treatments is compelling. Platinum salts (e.g., carboplatin, cisplatin, and oxaliplatin) are old drugs still used to treat BC, especially the triple-negative subgroup. However, only a subset of patients see a concrete benefit from these drugs, raising the question of how to select them properly. Therefore, predictive biomarkers for platinum salts in BC still represent an unmet clinical need. Here, we review clinical and preclinical works in order to summarize the current evidence about predictive or putative platinum salt biomarkers in BC. The association between gene mutations and platinum sensitivity has been largely described. However, beyond the mutations of these two genes, several other proteins belonging to the homologous recombination pathways have been linked to platinum response, defining the concept of BRCAness. Several works, here reviewed, have tried to capture BRCAness through different strategies, such as homologous recombination deficiency (HRD) score and genetic signatures. Moreover, p53 and its family members (p63 and p73) might also be used as predictors of platinum response. Finally, we describe the mounting preclinical evidence regarding base excision repair deficiency as a possible new platinum biomarker.
乳腺癌（BC）是女性中最常见的肿瘤死因，改善其治疗方法迫在眉睫。铂盐（如卡铂、顺铂和奥沙利铂）是仍用于治疗 BC 的老药，尤其是三阴性亚组。然而，只有一部分患者从这些药物中获得了确切的益处，这就提出了如何正确选择它们的问题。因此，BC 中铂盐的预测性生物标志物仍然是一个未满足的临床需求。在这里，我们回顾了临床和临床前的研究工作，以总结关于 BC 中预测性或推测性铂盐生物标志物的现有证据。基因突变与铂类药物敏感性之间的关联已被广泛描述。然而，除了这两个基因的突变外，其他几个属于同源重组途径的蛋白质也与铂类药物的反应相关，定义了 BRCAness 的概念。这里回顾的几项研究试图通过不同的策略来捕捉 BRCAness，如同源重组缺陷（HRD）评分和遗传特征。此外，p53 及其家族成员（p63 和 p73）也可用作铂类药物反应的预测因子。最后，我们描述了关于碱基切除修复缺陷作为一种新的可能的铂类药物生物标志物的不断增加的临床前证据。
