Department of Oncology, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 976/3, 77515 Olomouc, Czech Republic.
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 32300 Pilsen, Czech Republic.
Int J Mol Sci. 2018 Mar 15;19(3):868. doi: 10.3390/ijms19030868.
The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome.
食管癌(EC)的预后较差,尽管实验科学家和临床医生都付出了相当大的努力。新辅助放化疗后手术的三联治疗方法几十年来一直是金标准,但近年来并没有取得显著进展。缺乏合适的预后因素来指示哪些患者将从这种三联治疗中受益。一些患者在新辅助放化疗中迅速进展,因此这种治疗方法毫无用处,有时甚至有害。与此同时,其他患者在新辅助放化疗后实现完全缓解,随后的手术可能会增加他们发病和死亡的风险。患者的预后从极好到极差不等。考虑到这些差异,与其他因素相比,药物代谢酶和转运体在 EC 对化疗的反应中的作用可能更为重要,例如在胰腺癌中,无论治疗或疾病阶段如何,所有患者在化疗中都会进展。这篇综述调查了描述 ABC 转运体、遗传多态性、表观遗传调控和表型变化在 EC 预后和治疗中的潜在作用的已发表文献。该综述为进一步研究潜在的预测生物标志物提供了知识库,这些标志物将允许将患者分层到特定组中以获得最佳治疗效果。