Goodspeed Andrew, Jean Annie, Theodorescu Dan, Costello James C
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
University of Colorado Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Bladder Cancer. 2018 Jul 30;4(3):269-282. doi: 10.3233/BLC-170161.
Bladder cancer remains a cancer type in need of novel and alternative therapies. While multiple inhibitors of EGFR have been evaluated for efficacy in bladder cancer, the results have largely been disappointing with few patients responding to these therapies. Yet, there is a subset of patients that positively responds to EGFR inhibition with tumor shrinkage, indicating it is an effective treatment for a targeted set of bladder tumors.
To derive a gene expression signature capable of predicting the response to EGFR inhibition in bladder cancer cell lines.
he response to cetuximab for 68 colorectal cancer patients was used as training data to generate a gene expression signature. We applied this signature to bladder cancer cell lines and predictions were compared to the responses to seven EGFR inhibitors.
A novel 67-gene signature derived from colorectal cancer was able to significantly identify bladder cancer cell lines by their response to several EGFR inhibitors.
The 67-gene signature can determine bladder cancer cell line sensitivity to EGFR inhibition. This work demonstrates a preclinical strategy to identify bladder cancer cell lines for EGFR-targeted therapy.
膀胱癌仍然是一种需要新型和替代疗法的癌症类型。虽然已经评估了多种表皮生长因子受体（EGFR）抑制剂在膀胱癌中的疗效，但结果大多令人失望，很少有患者对这些疗法有反应。然而，有一部分患者对EGFR抑制有积极反应，肿瘤缩小，这表明它对一组特定的膀胱肿瘤是一种有效的治疗方法。
推导一种能够预测膀胱癌细胞系对EGFR抑制反应的基因表达特征。
将68例结直肠癌患者对西妥昔单抗的反应用作训练数据，以生成基因表达特征。我们将此特征应用于膀胱癌细胞系，并将预测结果与对七种EGFR抑制剂的反应进行比较。
从结直肠癌中得出的一种新的67基因特征能够通过膀胱癌细胞系对几种EGFR抑制剂的反应来显著识别它们。
67基因特征可以确定膀胱癌细胞系对EGFR抑制的敏感性。这项工作展示了一种用于识别适合EGFR靶向治疗的膀胱癌细胞系的临床前策略。
