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, G KM, K SA, S WE, Z KB, #REF! S#. Vascular heterogeneity influences treatment response in pancreatic cancer. 2025; (18):A127.
Document Type
Conference Proceeding
Publication Date
9-28-2025
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.
Issue
18
First Page
A127
