Irinotecan, a topoisomerase I inhibitor, has been widely used in the treatment of various solid tumors, including colorectal, lung, and pancreatic cancers. However, its efficacy is often limited by the development of resistance mechanisms within cancer cells. Understanding these resistance mechanisms is crucial for improving treatment outcomes and developing effective therapeutic strategies. This review article provides a comprehensive overview of the mechanisms underlying irinotecan resistance in cancer. Key resistance mechanisms discussed include the overexpression of drug efflux pumps, activation of DNA repair pathways, altered drug metabolism, and microenvironmental factors. Clinical implications, challenges, and emerging opportunities in overcoming irinotecan resistance are also explored, including the identification of biomarkers predictive of response/resistance, combination therapies targeting multiple resistance pathways, and advancements in drug delivery systems. By elucidating the complexities of irinotecan resistance, this review aims to inform future research directions and facilitate the development of personalized treatment approaches for patients with resistant cancers.
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