What is the clinical evidence from this study?

Study design: Other. Population: Pancreatic ductal adenocarcinoma (PDAC) (n=15). Intervention: PDAC patient-derived xenograft (PDX) implantation vs. Sham surgery. Primary outcome: Left ventricular compliance (EDPVR) (p=0.02).

What question did this study set out to answer?

To assess the impact of pancreatic adenocarcinoma on cardiac structure and function using a representative animal model.

April 5, 2026

Abstract 5226: The role of pancreatic adenocarcinoma cancer-stromal interactions on cardiac structure and function

Key Result

Orthotopic implantation of a PDAC patient-derived xenograft in mice significantly impaired left ventricular compliance compared to sham controls (EDPVR 1.06 vs 0.22; p=0.02).

Key Points

To assess the impact of pancreatic adenocarcinoma on cardiac structure and function using a representative animal model.
Implanted patient-derived xenografts into NSG mice both heterotopically and orthotopically, alongside sham surgeries as controls.
Monitored tumor volumes weekly until reaching a specific size for further cardiac assessments.
Conducted echocardiography and Millar catheterization to evaluate cardiac structure and function across the groups.
Collected cardiac and muscle tissues for histological and molecular analyses, including RNA sequencing.
Global longitudinal strain measures remained within normal values, but a trend of decline was observed in the orthotopic group.
Significant impairment in left ventricular compliance was noted, particularly in the orthotopic group compared to controls (p=0.02).
Early signs of systolic impairment and potential diastolic dysfunction were identified in mice with tumor burden, indicating a connection between cancer and cardiac decline.

Structured PICO

Does pancreatic ductal adenocarcinoma tumor burden induce cardiac remodeling and dysfunction in a preclinical mouse model?

Population

15 NSG mice

Intervention

Implantation of pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (PDX) heterotopically (n=5) or orthotopically (n=5)

Comparator

Sham surgeries (n=5)

Outcome

Cardiac structure and function assessed by echocardiography (GLS) and Millar catheterization (EDPVR) when tumor volume reached 1.5cmsurrogate

In a preclinical mouse model, pancreatic ductal adenocarcinoma tumor burden is associated with early diastolic dysfunction as evidenced by increased left ventricular stiffness.

Main Result

Absolute Event Rate: 1.06% vs 0.22%

p-value: p=0.02

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival of 13% despite advances in therapy. Patients with PDAC also experience significantly lower cardiac-specific median survival compared to those with other GI cancers. While cancer cachexia impacts survival through skeletal muscle loss, the contribution of cardiac function to outcomes in PDAC is unknown. We aim to evaluate cardiac tissue structure and function in the most representative human preclinical model. This will provide insight into cardiac remodeling associated with PDAC and its clinical implication for possible interventions to improve overall survival. We implanted a PDAC patient-derived xenograft (PDX) into five NSG mice heterotopically and five NSG mice orthotopically, with five NSG mice receiving sham surgeries as controls. Tumor volumes were monitored weekly and once reaching 1.5cm, echocardiography and Millar catheterization were performed to assess cardiac structure and function between the three groups. Cardiac muscle, gastrocnemius muscle and tumors were collected for histologic and molecular analysis, including staining for structural assessment RNA sequencing to assess for changes associated with tumor burden, which is ongoing. An ANOVA and simple unpaired t-test were used with a significance value set at p 0.05.Global longitudinal strain (GLS) measured by echocardiogram was within the normal values (-18 to -25%) across the groups, with no significant difference between the means of the sham (−20.3%), heterotopic (−21.2%), and orthotopic (−19.9%) groups. However, there is a slight trend showing a decline in GLS in the orthotopic group compared to the control group. The PV Loop data show a decline in left ventricular compliance (EDPVR) means in the heterotopic group (0.86) and orthotopic group (1.06) compared to the control group (0.22). The orthotopic group EDPVR mean is statistically different from the control group mean, with a simple unpaired t-test p-value of 0.02. The slight reduction in GLS observed in the orthotopic group relative to controls may indicate the presence of early systolic impairment in PDAC-bearing mice. Additionally, the results suggest that tumor burden is associated with impaired EDPVR, with the orthotopic group showing more stiffening as evidenced by a significantly elevated EDPVR when compared to the control group. This may indicate early diastolic dysfunction in the context of tumor related cardiac remodeling. We also anticipate that PDAC bearing mice will exhibit cardiac tissue remodeling, characterized by histological changes and transcriptional alterations linking cardiac decline and cancer progression. Recognizing early cardiac changes in patients with PDAC will help identify interventions that may ultimately improve treatment tolerance and clinical outcomes. Citation Format: Anna E. Gibson, Praveen Bhoopathi, Adolfo Mauro, Eleonora Mezzaroma, Vignesh Vudatha, Arunima Punjala, Vashti L. Bandy, Fadi Salloum, Jose G. Trevino. The role of pancreatic adenocarcinoma cancer-stromal interactions on cardiac structure and function abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5226.

Bookmark