Reply to ‘C-CAT's triumph in gastroenterology: the wisdom of cats is infinitely superior’

Excerpt

We greatly appreciate the Journal of Gastroenterology’s policy of providing an open opportunity to discuss unresolved scientific issues. We express our gratitude to Dr. Enomoto for his knowledgeable comments and meaningful questions on our study. As we mentioned in the main text, we consider the high prevalence of homologous recombination repair (HRR)-related genes being the primary reason for the more favorable outcomes in acinar cell carcinoma (ACC) patients receiving FOLFIRINOX compared with GEM + nab-PTX; however, the fact that FOLFIRINOX led to better outcomes than GEM + nab-PTX even in ACC patients without HRR genes was surprising to us as well. In line with other reports, Glazer et al. performed a systematic review and demonstrated that combination fluoropyrimidine-based regimens led to a higher disease control rate in ACC patients compared with gemcitabine-based regimens (60 vs. 28%, respectively) [1]. Xu et al. reported that fluoropyrimidine monotherapy was associated with a better treatment response than gemcitabine monotherapy, which indicates that this trend could be observed regardless of the concomitant use of platinum-based drugs [2]. Although the underlying mechanism remains unknown, it may be interesting to approach it from the perspective of drug metabolism. For example, the nucleoside transporter Human Equilibrative Nucleoside Transporter-1 (hENT-1), which plays a major role in the uptake of gemcitabine, has been studied as a potential biomarker for the anticancer activity of gemcitabine in patients with pancreatic ductal adenocarcinoma (PDAC). Indeed, several studies reported that higher expression levels of hENT-1 were correlated with longer overall survival in PDAC patients in adjuvant setting [3, 4]. Moreover, enzymes such as deoxycytidine kinase (dCK), cytidine deaminase (CDA), and nucleotidase (NT5C1A/NT5C3) are also known to significantly affect the sensitivity of cancer cells to gemcitabine [4]. Studies to clarify the characteristics of ACC based on genetic profiles related to drug metabolism have yet to be conducted. The future of cancer genome medicine should involve promoting comprehensive genomic analysis by whole genome sequencing, as well as sequencing cancer-related genes, which will contribute to the discoveries of optimal treatments. …