Vascular heterogeneity influences treatment response in pancreatic cancer
Recommended Citation
Kemp SB, Sullivan WB, Kahn BM, Sussman JH, Kim I, Katsuda T, Mahan S, Orlen MI, Zwernik SD, Hartway KM, Steele NG, Witkiewicz AK, Knudsen ES, Stanger BZ. Vascular heterogeneity influences treatment response in pancreatic cancer. Cancer Res 2025; 85(18):A127.
Document Type
Conference Proceeding
Publication Date
9-28-2025
Publication Title
Cancer Res
Keywords
Oncology
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, in part due to its heterogeneous tumor microenvironment. Most PDAC tumors are poorly vascularized and embedded within densely fibrotic stroma; however, in prior computational analyses, we identified a subset of PDAC tumors with hyper-vascular features. In this study, we sought to determine the extent of vascular heterogeneity in PDAC and its functional consequences. Analysis of human tumor specimens revealed that approximately 10-20% of human tumors display features of hyper-vascularity. Using a panel of clonal murine cell lines that recapitulate this heterogeneity, we demonstrate that VEGFA-mediated angiogenesis does not account for the increased vessel density. Functionally, we further show that hyper-vascular tumors display enhanced sensitivity to both chemotherapy and anti-angiogenic therapy. These findings help explain the limited efficacy of VEGFA-targeted therapies in unselected PDAC cohorts and highlight vessel density as a potential biomarker for patient stratification.
Volume
85
Issue
18
First Page
A127
