Faisal Muhammad Saleem, Hussain Imran, Ikram Muhammad Abdullah, Shah Syed Babar, Rehman Abdul, Iqbal Wajid
Department of Biological Sciences, International Islamic University, Islamabad, Pakistan.
Department of Biosciences, Nottingham Trent University, Loughborough, UK.
J Chemother. 2025 May;37(3):199-212. doi: 10.1080/1120009X.2024.2349444. Epub 2024 May 6.
Irinotecan is a critical anticancer drug used to treat metastatic colorectal cancer and advanced pancreatic ductal adenocarcinoma by obstructing topoisomerase 1; however, it can cause minor-to-severe and life-threatening adverse effects. UDP glucuronosyltransferase family 1 member A1 () polymorphisms increase the risk of irinotecan-induced neutropenia and diarrhea. Hence, screening for polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on and variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of genotype testing.
伊立替康是一种关键的抗癌药物，通过阻断拓扑异构酶1来治疗转移性结直肠癌和晚期胰腺导管腺癌；然而，它可能会引起从轻微到严重甚至危及生命的不良反应。尿苷二磷酸葡萄糖醛酸基转移酶1家族成员A1（）基因多态性会增加伊立替康诱导的中性粒细胞减少和腹泻的风险。因此，建议在基于伊立替康的化疗前筛查基因多态性，以将毒性降至最低，而脂质体有可能在胰腺导管腺癌患者中以较少的副作用递送伊立替康。本综述全面概述了伊立替康基因型指导给药对和变体的影响，纳入了药物基因组学研究、使用伊立替康治疗转移性结直肠癌和胰腺癌的最佳方案、降低毒性的指南以及对基因型检测成本效益的评估。
