Department of Urology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan.
Int J Mol Sci. 2018 Sep 15;19(9):2777. doi: 10.3390/ijms19092777.
Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have a favorable prognosis and quality of life with a preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting the clinical outcomes of chemoradiation-based BPT. The biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, the Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both the chemoradiation response and the prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients.
基于放化疗的膀胱保留治疗(BPT)目前是低危非转移性肌层浸润性膀胱癌(MIBC)患者的一种有治愈可能的选择,对于不适合接受根治性膀胱切除术(RC)的患者,BPT 也是一种替代方案。在 BPT 中,只有在放化疗后达到完全缓解(CR)的患者才有良好的预后和保留功能性膀胱的生活质量。因此,预测 CR 和良好的预后对于 BPT 的患者选择至关重要。我们回顾了预测基于放化疗的 BPT 临床结局的生物标志物。研究的生物标志物分为与细胞凋亡、细胞增殖、受体酪氨酸激酶、DNA 损伤反应基因、缺氧、分子亚型和其他相关的生物标志物。在这些生物标志物中,Ki-67 标记指数(Ki-67 LI)和减数分裂重组 11 可用于选择 BPT 或 RC。Ki-67 LI 和红细胞生成素受体 2(erbB2)可用于预测 BPT 患者的放化疗反应和预后。曲妥珠单抗与卡泊芬净和烟酰胺联合使用可以克服 erbB2 过表达和肿瘤缺氧导致的放化疗耐药性。需要进一步的研究来证实这些生物标志物在 MIBC 患者基于生物标志物的个体化管理中的实际应用价值。