化疗是癌症患者中广泛使用的一线治疗方法之一。然而，化疗耐药是癌症患者中最常见的问题之一，导致治疗失败和肿瘤复发。考虑到化疗药物在正常组织中的副作用，有必要研究与药物耐药有关的分子机制，以改善癌症患者的治疗策略。长链非编码RNA（lncRNA）在与药物耐药相关的细胞过程调控中起着重要作用。在多种化疗耐药肿瘤中，经常报道lncRNA的异常调控。吉西他滨（GEM）作为一种核苷类似物在不同癌症中有广泛的治疗应用。然而，GEM耐药被认为是治疗的挑战。考虑到lncRNA在GEM耐药发生中的作用，在本综述中我们讨论了lncRNA在癌症患者的GEM反应调控中的分子机制。据报道，通过直接或间接调控转录因子、自噬、Polycomb复合体以及PI3K/AKT、MAPK、WNT、JAK/STAT和TGF-β等信号通路，lncRNA主要具有诱导GEM耐药的致癌作用。本综述为将lncRNA作为非侵入性标志物以预测癌症患者的GEM反应铺平了道路。因此，lncRNA可以作为高效的标志物，降低GEM耐药癌症患者可能的化疗副作用，并为这些患者确定适当的治疗策略。©2023. BioMed Central Ltd.属于施普林格自然出版集团的一部分。

Chemotherapy is widely used as one of the first line therapeutic methods in cancer patients. However, chemotherapeutic resistance is one of the most common problems in cancer patients, which leads to the therapeutic failure and tumor relapse. Considering the side effects of chemotherapy drugs in normal tissues, it is required to investigate the molecular mechanisms involved in drug resistance to improve the therapeutic strategies in cancer patients. Long non-coding RNAs (lncRNAs) have pivotal roles in regulation of cellular processes associated with drug resistance. LncRNAs deregulations have been frequently reported in a wide range of chemo-resistant tumors. Gemcitabine (GEM) as a nucleoside analog has a wide therapeutic application in different cancers. However, GEM resistance is considered as a therapeutic challenge. Considering the role of lncRNAs in the occurrence of GEM resistance, in the present review we discussed the molecular mechanisms of lncRNAs in regulation of GEM response among cancer patients. It has been reported that lncRNAs have mainly an oncogenic role as the inducers of GEM resistance through direct or indirect regulation of transcription factors, autophagy, polycomb complex, and signaling pathways such as PI3K/AKT, MAPK, WNT, JAK/STAT, and TGF-β. This review paves the way to present the lncRNAs as non-invasive markers to predict GEM response in cancer patients. Therefore, lncRNAs can be introduced as the efficient markers to reduce the possible chemotherapeutic side effects in GEM resistant cancer patients and define a suitable therapeutic strategy among these patients.© 2023. BioMed Central Ltd., part of Springer Nature.