Witkiewicz Agnieszka K, Knudsen Erik S
Breast Cancer Res. 2014 May 7;16(3):207. doi: 10.1186/bcr3652.
A series of recent studies have demonstrated that the retinoblastoma tumor suppressor (RB) pathway plays a critical role in multiple clinically relevant aspects of breast cancer biology, spanning early stage lesions to targeted treatment of metastatic disease. In ductal carcinoma in situ, multiple groups have shown that dysregulation of the RB pathway is critically associated with recurrence and disease progression. Functional models have similarly illustrated key roles for RB in regulating epithelial-mesenchymal transition and other features contributing to aggressive disease. Invasive breast cancers are treated in distinct fashions, and heterogeneity within the RB pathway relates to prognosis and response to commonly used therapeutics. Luminal B breast cancers that have a poor prognosis amongst estrogen receptor-positive disease are defined based on the expression of RB-regulated genes. Such findings have led to clinical interventions that directly target the RB pathway through CDK4/6 inhibition which have promise in both estrogen receptor-positive and Her2-positive disease. In contrast, RB loss results in improved response to chemotherapy in triple-negative breast cancer, where ongoing research is attempting to define intrinsic vulnerabilities for targeted intervention. These findings support a wide-reaching impact of the RB pathway on disease that could be harnessed for improved clinical interventions.
一系列近期研究表明，视网膜母细胞瘤肿瘤抑制因子（RB）通路在乳腺癌生物学的多个临床相关方面发挥着关键作用，涵盖从早期病变到转移性疾病的靶向治疗。在导管原位癌中，多个研究团队已表明RB通路的失调与复发及疾病进展密切相关。功能模型同样阐明了RB在调节上皮-间质转化及其他导致侵袭性疾病的特征方面的关键作用。侵袭性乳腺癌的治疗方式各不相同，RB通路内的异质性与预后及对常用治疗方法的反应相关。在雌激素受体阳性疾病中预后较差的Luminal B型乳腺癌是根据RB调控基因的表达来定义的。这些发现促使了通过抑制CDK4/6直接靶向RB通路的临床干预措施的出现，这些措施在雌激素受体阳性和人表皮生长因子受体2（Her2）阳性疾病中均有前景。相比之下，RB缺失导致三阴性乳腺癌对化疗的反应改善，目前正在进行的研究试图确定可用于靶向干预的内在脆弱性。这些发现支持RB通路对疾病具有广泛影响，可用于改进临床干预措施。
