Funamizu Naotake, Honjo Masahiko, Tamura Kei, Sakamoto Katsunori, Ogawa Kohei, Takada Yasutsugu
Department of Hepatobiliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon 791-0295, Ehime, Japan.
Cancers (Basel). 2023 Feb 15;15(4):1230. doi: 10.3390/cancers15041230.
Despite extensive research, pancreatic cancer remains a lethal disease with an extremely poor prognosis. The difficulty in early detection and chemoresistance to therapeutic agents are major clinical concerns. To improve prognosis, novel biomarkers, and therapeutic strategies for chemoresistance are urgently needed. microRNAs (miRNAs) play important roles in the development, progression, and metastasis of several cancers. During the last few decades, the association between pancreatic cancer and miRNAs has been extensively elucidated, with several miRNAs found to be correlated with patient prognosis. Moreover, recent evidence has revealed that miRNAs are intimately involved in gemcitabine sensitivity and resistance through epithelial-to-mesenchymal transition, the tumor microenvironment, and drug metabolism. Gemcitabine is the gold standard drug for pancreatic cancer treatment, but gemcitabine resistance develops easily after chemotherapy initiation. Therefore, in this review, we summarize the gemcitabine resistance mechanisms associated with aberrantly expressed miRNAs in pancreatic cancer, especially focusing on the mechanisms associated with epithelial-to-mesenchymal transition, the tumor microenvironment, and metabolism. This novel evidence of gemcitabine resistance will drive further research to elucidate the mechanisms of chemoresistance and improve patient outcomes.
尽管进行了广泛的研究，但胰腺癌仍然是一种致命疾病，预后极差。早期检测困难和对治疗药物的化疗耐药性是主要的临床问题。为了改善预后，迫切需要新的生物标志物和化疗耐药性的治疗策略。微小RNA（miRNA）在几种癌症的发生、发展和转移中发挥着重要作用。在过去几十年中，胰腺癌与miRNA之间的关联已得到广泛阐明，发现几种miRNA与患者预后相关。此外，最近的证据表明，miRNA通过上皮-间质转化、肿瘤微环境和药物代谢密切参与吉西他滨的敏感性和耐药性。吉西他滨是胰腺癌治疗的金标准药物，但化疗开始后很容易产生吉西他滨耐药性。因此，在本综述中，我们总结了与胰腺癌中异常表达的miRNA相关的吉西他滨耐药机制，尤其关注与上皮-间质转化、肿瘤微环境和代谢相关的机制。这种关于吉西他滨耐药性的新证据将推动进一步的研究，以阐明化疗耐药机制并改善患者预后。
