TCGA-tpm，data

The development of cisplatin resistance often results in a grim prognosis in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established. Herein, we found that overactivation of SRC is associated with cisplatin-resistance. SRC activates hexokinase2 which up-regulates glycolysis and especially the pentose phosphate pathway that leading to increased nucleotide synthesis and NADPH production which can neutralize reactive oxygen species (ROS) induced by cisplatin, thereby protecting bladder cancer cells from cisplatin-induced DNA damage. This phenomenon was effectively reversed by knockout of SRC and inhibition of SRC activity by the SRC inhibitor, eCF506. Moreover, we constructed Cell-derived xenograft (CDX) and Patient-derived xenograft (PDX) from cisplatin-resistant bladder cancer patient. eCF506 exhibited excellent anti-tumor effects and effectively enhanced cisplatin-sensitivity. Altogether, our findings demonstrate that targeting SRC is a promising approach to overcome cisplatin-resistance in bladder cancer.

顺铂耐药的发生常导致晚期或复发性膀胱癌患者预后不佳，目前针对顺铂耐药的有效治疗策略尚未得到充分确立。本研究发现，SRC的过度激活与顺铂耐药密切相关。SRC可激活己糖激酶2（hexokinase 2），进而上调糖酵解进程，尤其激活磷酸戊糖途径，最终促进核苷酸合成与还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的生成；NADPH可中和顺铂诱导产生的活性氧（ROS），从而保护膀胱癌细胞免受顺铂介导的DNA损伤。上述现象可通过敲除SRC基因，或使用SRC抑制剂eCF506抑制其活性得到有效逆转。此外，本研究从顺铂耐药的膀胱癌患者样本中构建了细胞源性异种移植模型（Cell-derived xenograft, CDX）与患者源性异种移植模型（Patient-derived xenograft, PDX），实验结果显示eCF506具有优异的抗肿瘤活性，并可有效增强肿瘤对顺铂的敏感性。综上，本研究结果证实，靶向SRC是克服膀胱癌顺铂耐药的极具潜力的治疗策略。

搜集汇总

背景与挑战

背景概述

该数据集研究了膀胱癌中顺铂耐药的分子机制，重点关注SRC基因通过调节糖酵解和磷酸戊糖途径促进耐药的机制，并包含相关实验数据。数据集包含多个实验数据文件，涉及细胞活力、代谢物分析等。