Abstract 3050: Evaluating the role of ∆Np63α in driving growth and metastasis of pancreatic ductal adenocarcinoma

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the US and is rising in incidence. PDAC tumors may be either classical or basal in transcriptomic subtype, and PDAC patients with basal tumors have worse prognosis and may have increased resistance to chemotherapy. Previous studies have shown that ∆Np63α drives basal program expression. The goal of this project is to investigate whether ∆Np63α expression is sufficient to increase pancreatic cancer cell growth, metastasis and chemoresistance and whether these cells can outcompete ∆Np63α non-expressers in mixed tumors. Non-∆Np63α expressing human PDAC cell lines AsPC1 and HPAFII were stably transduced to express either ∆Np63α or mCherry (control). For both AsPC1 and HPAFII, ∆Np63α-expressing and control cells had similar proliferation rates and susceptibility to chemotherapy agents oxaliplatin and SN38 when grown in culture. When control or ∆Np63α-expressing AsPC1 cells were implanted orthotopically into the pancreas of athymic nude mice, there was no significant difference in primary tumor mass and pathological analysis of lungs and livers did not reveal any significant difference in metastatic burden. Bulk RNA sequencing of primary tumors confirmed that tumors in mice inoculated with AsPC1-∆Np63α had significantly upregulated expression of genes associated with the basal subtype. Collectively, these data suggest that while ∆Np63α drives the basal program in PDAC, its expression is insufficient to cause resistance to these chemotherapies or a growth or metastatic advantage in an immunodeficient setting. Further work is needed to elucidate the mechanism by which ∆Np63α contributes to more aggressive PDAC tumors. Citation Format: Daniel H. Ryan, Chin-Hsien (Emily) Tai, Xianyu Zhang, Mayrel Palestino Dominguez, Christine Alewine. Evaluating the role of ∆Np63α in driving growth and metastasis of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3050.