Comment on “Deciphering pathogenic mechanisms of BDCPP exposure in endometrial cancer progression via an integrated approach combining network toxicology, machine learning, and molecular docking”

To the Editor, I read with great interest the study by Wang et al titled “Deciphering pathogenic mechanisms of BDCPP exposure in endometrial cancer progression via an integrated approach combining network toxicology, machine learning, and molecular docking” recently published in the International Journal of Surgery, which elucidates the pathogenic mechanisms by which bis(1,3-dichloro-2-propyl) phosphate (BDCPP) exposure promotes endometrial cancer (EC) progression1. The authors have utilized a robust multi-omics approach to identify ESR1 and VEGFA as central nodes in BDCPP-induced malignancy. This research is timely, as it bridges environmental toxicology with surgical oncology, yet several points regarding its clinical translation for surgeons warrant further discussion. The identification of BDCPP as an environmental driver of EC has significant implications for postoperative risk stratification. In current surgical practice, prognosis is largely determined by FIGO staging and histological grading. However, findings by Wang et al suggest that environmental exposure history could be a hidden variable. For patients undergoing hysterectomy, it would be insightful to investigate whether high systemic levels of BDCPP correlate with lymphovascular space invasion or occult lymph node metastasis, as environmental endocrine disruptors have been linked to increased invasiveness in other hormone-dependent tumors2. If such a correlation exists, BDCPP levels could potentially help surgeons decide between radical versus fertility-sparing surgery. The study highlights ESR1 as a primary target. Since endocrine therapy is a cornerstone for many EC patients, particularly those desiring fertility preservation, the interference of environmental disruptors with estrogen receptor signaling is concerning. Recent evidence suggests that exposure to organophosphate flame retardants can alter the therapeutic efficacy of hormonal agents3. Clarifying whether patients with high BDCPP exposure require escalated hormonal treatment or adjuvant anti-VEGF therapy (targeting the identified VEGFA node) would be a valuable step toward personalized management. While molecular docking provided insights into the BDCPP-ESR1 interaction, the spatial toxicological effect within the uterine microenvironment remains unexplored. We suggest that future studies employ spatial transcriptomics to visualize the recruitment of angiogenic factors at the tumor-stroma interface4. This would provide surgeons with a “molecular map” of how environmental toxins reshape the surgical landscape. Conclusion In summary, Wang et al provide a compelling roadmap for understanding how ubiquitous pollutants fuel EC progression. Integrating toxicological data into clinical surgical frameworks will undoubtedly enhance our ability to predict recurrence and tailor treatment for EC patients.