Clinical efficacy and chemoresistance analysis of precision neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a prospective, single-arm pilot study

作者：Yonggang He, Yinan Zhu, Weiwei Wang, Yuqing Yi, Zheng Wang, Chongyu Zhao, Jing Li, Xiaobing Huang, Lu Zheng · 发表于：International Journal of Surgery · 年份：2025 · DOI：10.1097/js9.0000000000002342 · 被引用次数：9 · 研究领域：Pancreatic and Hepatic Oncology Research、Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer Cells and Metastasis

BACKGROUND: Neoadjuvant chemotherapy (NAC) can improve the survival outcomes of patients with pancreatic cancer, but for borderline resectable pancreatic cancer (BRPC) the proportion of conversion to surgery remains unsatisfactory. This single-arm pilot study aimed to assess the clinical efficacy and safety of NAC based on patient-derived organoids (PDOs) for BRPC. METHODS: Biopsy samples from BRPC patients were collected for generating PDOs. Gemcitabine plus nab-paclitaxel as NAC was initially administrated for one cycle, and then the treatment regimen was adjusted based on the PDO drug sensitivity testing. The primary endpoint was the objective response rate (ORR). Secondary endpoints included R0 resection rate, NAC-related adverse events (AEs), and postoperative complications. Exploratory objectives were to assess the chemoresistance to gemcitabine. RESULTS: Totally 19 of 25 patients were eligible for the study, among whom 16 achieved partial response and received surgical resection, with the ORR of 84.2% (16/19). The R0 resection rate was 81.3% (13/16). During NAC, 8 (42.1%, 8/19) patients experienced different grades of AEs, mainly including grade 2 myelosuppression (26.3%), cutaneous pruritus (5.3%), and diarrhea (5.3%). scRNA-seq analysis of duct cells showed that the transcriptome in aneuploid cells may affect gemcitabine resistance via multiple pathways, among which upregulation of drug-resistant genes ( OLFM4, AGR2, MUC5AC, MUC1, HMGA1, REG4, IL17RB, GCNT3, AKR1B10,...