TY - JOUR T1 - CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer JF - Anticancer Research JO - Anticancer Res SP - 697 LP - 707 DO - 10.21873/anticanres.15528 VL - 42 IS - 2 AU - TOSHIAKI HAGIWARA AU - KIICHI SUGIMOTO AU - HIROTAKA MOMOSE AU - TAKAHIRO IRIE AU - KUMPEI HONJO AU - YU OKAZAWA AU - MASAYA KAWAI AU - SHINGO KAWANO AU - SHINYA MUNAKATA AU - MAKOTO TAKAHASHI AU - YUTAKA KOJIMA AU - NOBUKO SERIZAWA AU - AKIHITO NAGAHARA AU - ROBERT M. HOFFMAN AU - MALCOLM V. BROCK AU - KAZUHIRO SAKAMOTO Y1 - 2022/02/01 UR - http://ar.iiarjournals.org/content/42/2/697.abstract N2 - Background/Aim: We investigated whether promoter methylation of the checkpoint-with-forkhead-and-ring-finger-domains (CHFR) gene is a predictor of the efficacy of irinotecan-based systemic chemotherapy for advanced colorectal cancer (CRC) patients. Materials and Methods: CHFR-promoter methylation was measured by quantitative methylation-specific PCR (qMSP). The histoculture drug response assay (HDRA) was used in vitro to analyze the correlation between CHFR-promoter methylation and the efficacy of the irinotecan-active-metabolite SN38 in colorectal-cancer tissues from 44 CRC patients. CHFR promoter-methylation was also analyzed for its correlation with clinical response to irinotecan-based systemic chemotherapy of 49 CRC patients. Results: CHFR-promoter methylation significantly-positively correlated with inhibition of colon cancer by SN38 in the HDRA (p=0.002). CHFR-promoter methylation also significantly-positively correlated with clinical response to irinotecan-based systemic chemotherapy (p=0.04 for disease control). CHFR-promoter methylation also significantly-positively correlated (p=0.01) with increased progression-free survival for patients treated with irinotecan-containing FLOFIRI in combination with bevacizumab, the most-frequent regimen in the cohort. Conclusion: Sensitivity of advanced CRC patients to irinotecan-based systemic chemotherapy can be predicted by the extent of CHFR-promoter methylation. ER -