DiStefano Johanna K, Davis Bethany
Diabetes and Fibrotic Disease Unit, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ 85004, USA.
Cancers (Basel). 2019 Apr 5;11(4):486. doi: 10.3390/cancers11040486.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although diagnostic measures and surgical interventions have improved in recent years, the five-year survival rate for patients with advanced HCC remains bleak-a reality that is largely attributable to an absence of early stage symptoms, lack of adequate diagnostic and prognostic biomarkers, and the common occurrence of acquired resistance to chemotherapeutic agents during HCC treatment. A limited understanding of the molecular mechanisms underlying HCC pathogenesis also presents a challenge for the development of specific and efficacious pharmacological strategies to treat, halt, or prevent progression to advanced stages. Over the past decade, aldo-keto reductase family 1 member 10 (AKR1B10) has emerged as a potential biomarker for the diagnosis and prognosis of HCC, and experimental studies have demonstrated roles for this enzyme in biological pathways underlying the development and progression of HCC and acquired resistance to chemotherapeutic agents used in the treatment of HCC. Here we provide an overview of studies supporting the diagnostic and prognostic utility of AKR1B10, summarize the experimental evidence linking AKR1B10 with HCC and the induction of chemoresistance, and discuss the clinical value of AKR1B10 as a potential target for HCC-directed drug development. We conclude that AKR1B10-based therapies in the clinical management of specific HCC subtypes warrant further investigation.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。尽管近年来诊断措施和外科干预有所改善，但晚期HCC患者的五年生存率仍然很低——这一现实很大程度上归因于缺乏早期症状、缺乏足够的诊断和预后生物标志物，以及HCC治疗期间化疗药物获得性耐药的普遍发生。对HCC发病机制潜在分子机制的有限理解也给开发治疗、阻止或预防进展到晚期的特异性和有效药理学策略带来了挑战。在过去十年中，醛酮还原酶家族1成员10（AKR1B10）已成为HCC诊断和预后的潜在生物标志物，实验研究表明该酶在HCC发生发展和化疗药物获得性耐药的生物学途径中发挥作用。在此，我们概述了支持AKR1B10诊断和预后效用的研究，总结了将AKR1B10与HCC及化疗耐药诱导相关的实验证据，并讨论了AKR1B10作为HCC靶向药物开发潜在靶点的临床价值。我们得出结论，基于AKR1B10的疗法在特定HCC亚型的临床管理中值得进一步研究。
