Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment.
Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment.
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最近对5-氟尿嘧啶的抗性机制和结肠癌治疗中的逆转策略的最新消息。
DOI：
10.3390/biology10090854
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发表时间：
2021-08-31
期刊：
影响因子：
4.2
通讯作者：
Mohtarrudin N
中科院分区：
文献类型：
--
作者：
Azwar S;Seow HF;Abdullah M;Faisal Jabar M;Mohtarrudin N
癌细胞对化疗的获得性耐药是化疗失败的主要因素，最终导致疾病进展和死亡。最近的研究提供了令人信服的证据，证明癌细胞产生耐药性的各种机制和途径。本文综述了与5-FU耐药有关的机制，并讨论了正在进行的预防癌细胞化疗耐药和使其对癌症药物重新敏感的努力。5-氟尿嘧啶(5-FU) +亚叶酸钙（LV）仍然是早期结肠癌的主要标准辅助化疗方案，也是转移性结肠癌患者联合奥沙利铂（FOLFOX）或伊立替康（FOLFIRI）方案的首选一线选择。尽管治疗取得了一定程度的成功，但仍有许多患者报告了因化疗耐药而导致化疗失败的发生率。这种耐药性可以定义为肿瘤对化疗的耐受性，无论是内在的还是获得性的，主要是由不同途径中各种成分的失调所驱动的。近年来，已经确定5-FU耐药的发生与多药耐药类似，可归因于药物转运的改变、细胞凋亡的逃避、细胞周期和dna损伤修复机制的改变、自噬的调节、上皮-间质转化、癌症干细胞的参与、肿瘤微环境相互作用、miRNA失调、表观遗传改变以及氧化还原失衡。5- fu特异性的某些抗性机制也被确定为胸腺嘧啶合成酶、二氢嘧啶脱氢酶、亚甲基四氢叶酸还原酶的上调和胸腺嘧啶磷酸化酶的下调。事实上，这些机制的成功调节已经成为许多研究的游戏计划，这些研究使用小分子抑制剂，基于植物的小分子和非编码RNA调节剂来有效逆转结肠癌细胞中的5-FU耐药性。希望这些研究能够为我们在不久的将来开发新的药物提供基础知识，这些药物将与5-FU协同作用，增强其抗肿瘤作用，提高患者的总体生存率。
Acquired resistance to chemotherapy by cancer cells is the predominant factor in chemotherapy failure, which ultimately leads to disease progression and death. Recent studies have presented compelling evidence of the various mechanisms and pathways through which cancer cells have developed resistance to drugs. This review summarises the mechanisms pertaining to 5-FU resistance and discusses ongoing efforts to prevent chemotherapy resistance in cancer cells and to re-sensitise them to cancer drugs. 5-Fluorouracil (5-FU) plus leucovorin (LV) remain as the mainstay standard adjuvant chemotherapy treatment for early stage colon cancer, and the preferred first-line option for metastatic colon cancer patients in combination with oxaliplatin in FOLFOX, or irinotecan in FOLFIRI regimens. Despite treatment success to a certain extent, the incidence of chemotherapy failure attributed to chemotherapy resistance is still reported in many patients. This resistance, which can be defined by tumor tolerance against chemotherapy, either intrinsic or acquired, is primarily driven by the dysregulation of various components in distinct pathways. In recent years, it has been established that the incidence of 5-FU resistance, akin to multidrug resistance, can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery, regulation of autophagy, epithelial-to-mesenchymal transition, cancer stem cell involvement, tumor microenvironment interactions, miRNA dysregulations, epigenetic alterations, as well as redox imbalances. Certain resistance mechanisms that are 5-FU-specific have also been ascertained to include the upregulation of thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, and the downregulation of thymidine phosphorylase. Indeed, the successful modulation of these mechanisms have been the game plan of numerous studies that had employed small molecule inhibitors, plant-based small molecules, and non-coding RNA regulators to effectively reverse 5-FU resistance in colon cancer cells. It is hoped that these studies would provide fundamental knowledge to further our understanding prior developing novel drugs in the near future that would synergistically work with 5-FU to potentiate its antitumor effects and improve the patient’s overall survival.
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影响因子：
5.9
作者：
Bower JJ;Vance LD;Psioda M;Smith-Roe SL;Simpson DA;Ibrahim JG;Hoadley KA;Perou CM;Kaufmann WK
通讯作者：
Kaufmann WK
影响因子：
3.7
作者：
Botticelli, Andrea;Borro, Marina;Mazzuca, Federica
通讯作者：
Mazzuca, Federica
影响因子：
5.8
作者：
Al-Obeed, Omar;El-Obeid, Adila Salih;Abdulla, Maha-Hamadien
通讯作者：
Abdulla, Maha-Hamadien
影响因子：
3.6
作者：
Angius, Andrea;Pira, Giovanna;De Miglio, Maria Rosaria
通讯作者：
De Miglio, Maria Rosaria
影响因子：
4.7
作者：
Benhalilou, Nehia;Alsamri, Halima;Iratni, Rabah
通讯作者：
Iratni, Rabah