{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim J"],"funding":["National Research Foundation of Korea"],"pagination":["3385"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11475853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(19)"],"pubmed_abstract":["<b>Background/Objectives</b>: Irinotecan, a camptothecin (CPT) derivative, is commonly used as a first-line therapy for colorectal cancer (CRC), but resistance remains a significant challenge. This study aims to explore the therapeutic potential of FL118, another CPT derivative, with a focus on overcoming resistance to irinotecan. <b>Methods:</b> The effects of FL118 on CRC cells were evaluated, and bioinformatics analysis was performed on RNA-seq data. Transfection was conducted to observe the knockdown effect of survivin, and the in vivo efficacy of FL118 was assessed using a xenograft model. <b>Results</b>: FL118 induces apoptosis, G2/M arrest, and DNA damage. A notable mechanism of action of FL118 is a reduction in survivin levels, which downregulates the expression of RAD51, a key marker of homologous recombination, and attenuates DNA repair processes. Given that SN38 is the active metabolite of irinotecan, FL118 reduces cell viability and RAD51 in SN38-resistant LOVO cells. <b>Conclusions</b>: Our findings provide effective insights into the antitumor activity of FL118 and its potential as a therapeutic agent for overcoming irinotecan resistance in CRC."],"journal":["Cancers"],"pubmed_title":["FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin-RAD51 Downregulation."],"pmcid":["PMC11475853"],"funding_grant_id":["2022R1A2C2004738"],"pubmed_authors":["Jeong Y","Kim SE","Shin SJ","Kim J","Shin YM"],"additional_accession":[]},"is_claimable":false,"name":"FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin-RAD51 Downregulation.","description":"<b>Background/Objectives</b>: Irinotecan, a camptothecin (CPT) derivative, is commonly used as a first-line therapy for colorectal cancer (CRC), but resistance remains a significant challenge. This study aims to explore the therapeutic potential of FL118, another CPT derivative, with a focus on overcoming resistance to irinotecan. <b>Methods:</b> The effects of FL118 on CRC cells were evaluated, and bioinformatics analysis was performed on RNA-seq data. Transfection was conducted to observe the knockdown effect of survivin, and the in vivo efficacy of FL118 was assessed using a xenograft model. <b>Results</b>: FL118 induces apoptosis, G2/M arrest, and DNA damage. A notable mechanism of action of FL118 is a reduction in survivin levels, which downregulates the expression of RAD51, a key marker of homologous recombination, and attenuates DNA repair processes. Given that SN38 is the active metabolite of irinotecan, FL118 reduces cell viability and RAD51 in SN38-resistant LOVO cells. <b>Conclusions</b>: Our findings provide effective insights into the antitumor activity of FL118 and its potential as a therapeutic agent for overcoming irinotecan resistance in CRC.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-04T01:17:22.649Z","creation":"2025-04-04T01:17:22.649Z"},"accession":"S-EPMC11475853","cross_references":{"pubmed":["39410005"],"doi":["10.3390/cancers16193385"]}}