Core Viewpoint - The study identifies AKR1B1 as a key regulatory enzyme in metabolic reprogramming and a potential biomarker and therapeutic target for hepatocellular carcinoma (HCC), suggesting that targeting AKR1B1 can reverse systemic therapy resistance in HCC [3][7]. Group 1: Research Findings - HCC is a major subtype of liver cancer and a leading cause of cancer-related deaths globally, with high incidence and mortality rates [2]. - The research team established HCC cell lines with multidrug resistance characteristics, observing enhanced metabolic activity in these cells [5]. - Multi-omics analysis revealed that glucose-lipid and glutathione metabolic pathways are overactive, playing critical roles in supporting tumor cell proliferation and survival [5]. Group 2: Mechanism of Resistance - The study constructed a metabolic reprogramming map for resistant HCC cells, identifying AKR1B1 as a key regulatory factor that maintains resistance by modulating energy metabolism and enhancing stress tolerance [5]. - The expression level of AKR1B1 is closely related to drug resistance and poor prognosis in HCC patients, highlighting its predictive value [5]. Group 3: Therapeutic Implications - The combination of Epalrestat, a clinically approved AKR1B1 inhibitor, with standard therapy (Lenvatinib) significantly alleviated resistance in HCC [7]. - The findings provide new insights into the mechanisms of resistance in HCC and lay the theoretical foundation for developing new predictive biomarkers and therapeutic strategies to overcome resistance [7].

起初，那只是偶尔的腹部隐痛。周炜和妻子丹丹以为不过是肠胃炎在作祟。 然而，CT报告上的诊断结论像一记闷雷劈进他们的生活——结直肠癌肝转移，肝脏多发团块 状；较大位于肝左叶，大小约6 . 9 cmx 7 . 6 cm。 因已经没办法直接手术切除，那一刻起，这个家庭被推上了一条与时间赛跑的赛道。在经过 多周期高强度的化疗后，周炜的身体状态在2 0 2 4年4月突然急剧下降。 这个曾经能在化疗间隙和牌友搓几圈麻将的男人，开始被剧痛钉在床上。在因耐药更换治疗 药物后，他开始全身疼痛、吃不下东西，连呼吸都像在抽走所剩无几的力气。"很长一段时间 无法进食，实在是疼得无法翻身，整个人的状态很虚，气上不来。"周炜的妻子丹丹回忆时声 音低沉，似乎又看见丈夫蜷缩在病床上的样子。 已6 1岁的俞澄漪则是在2 0 2 2年的冬天确诊为原发性肝癌，肝内较大的病灶约5厘米。俞澄漪的 女儿则回忆起，最开始母亲做了化疗，但化疗效果并不理想。恶心、呕吐、乏力……一次次 难熬的化疗过程，使得母亲开始排斥治疗，这种揪心的挣扎如同在暴风雨中守护一盏摇曳的 烛火。 生死竞速： 既是救火，亦是希望 武汉大学人民医院肝胆外科主任汪斌教授介绍，部分传统疗法 ...