RT Journal Article SR Electronic T1 CHFR-Promoter-Methylation Status Is Predictive of Response to Irinotecan-based Systemic Chemotherapy in Advanced Colorectal Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 697 OP 707 DO 10.21873/anticanres.15528 VO 42 IS 2 A1 TOSHIAKI HAGIWARA A1 KIICHI SUGIMOTO A1 HIROTAKA MOMOSE A1 TAKAHIRO IRIE A1 KUMPEI HONJO A1 YU OKAZAWA A1 MASAYA KAWAI A1 SHINGO KAWANO A1 SHINYA MUNAKATA A1 MAKOTO TAKAHASHI A1 YUTAKA KOJIMA A1 NOBUKO SERIZAWA A1 AKIHITO NAGAHARA A1 ROBERT M. HOFFMAN A1 MALCOLM V. BROCK A1 KAZUHIRO SAKAMOTO YR 2022 UL http://ar.iiarjournals.org/content/42/2/697.abstract AB 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.