Reply to ‘MDM2 amplification in advanced biliary tract cancer: something new to explore?’

Reply to 'MDM2 amplification in advanced biliary tract cancer: something new to explore?'We thank Rizzo and colleagues for their interest in our recent article, 'Molecular profile and clinical impact of MDM2 amplification in patients with advanced biliary tract cancer'. 1 As they correctly pointed out, our study was limited by its single-institution design and the predominance of East Asian ethnicity.We agree that this may affect the generalizability of our findings, given the potential geographic and ethnic heterogeneity 2,3 in the relationship between MDM2 amplification and the clinical behavior of biliary tract cancer (BTC).Nevertheless, this single-institution setting allowed us to carry out a meticulous correlative analysis under consistent conditions, avoiding heterogeneity in sequencing panels, standard of care, or the quality of retrospectively collected clinical data.Since BTC is a global disease with a genomic landscape that varies across races and regions, validation of our results in internationally representative cohorts is indeed an urgent need.We also agree that further studies are warranted to investigate the impact of MDM2 amplification in patients treated with current standard gemcitabine-cisplatin (Gem-Cis) plus immune checkpoint inhibitors (ICIs), [4][5][6] as most patients in our cohort received GemCis without ICIs.Despite these limitations, our work represents the first comprehensive study to assess both prevalence and prognostic impact of MDM2 amplification in BTC.Once again, we sincerely appreciate the thoughtful comments by Rizzo and colleagues and fully agree that international collaboration will be essential to further clarify the biological and clinical relevance of MDM2 amplification in BTC, particularly in the context of predictive biomarkers and new therapeutic targets.