# Focused Ultrasound in Pancreatic Ductal Adenocarcinoma: Mechanisms, Preclinical Evidence, and Emerging Clinical Applications

## TL;DR

Focused ultrasound shows potential as a non-invasive treatment for pancreatic cancer by targeting tumors, improving drug delivery, and boosting immune responses.

## Contribution

This review provides a comprehensive overview of focused ultrasound mechanisms and applications in pancreatic cancer treatment.

## Key findings

- Focused ultrasound can destroy tumor tissue and disrupt barriers that hinder drug delivery.
- FUS can stimulate immune responses and enhance the effectiveness of other therapies like chemotherapy and immunotherapy.
- Preclinical and early clinical studies show promise for integrating FUS into pancreatic cancer care.

## Abstract

Pancreatic ductal adenocarcinoma is one of the deadliest cancers, in part because its dense structure limits the effectiveness of chemotherapy, radiation, and immunotherapy. Focused ultrasound is a non-invasive technology that uses sound waves to precisely target tumors without surgery. Depending on how it is applied, focused ultrasound can destroy tumor tissue, disrupt physical barriers that block drug delivery, and stimulate immune responses against cancer. In recent years, focused ultrasound has shown promise in laboratory models and early clinical studies for pancreatic cancer. This review summarizes how focused ultrasound works, what has been learned from preclinical and clinical studies, and where the field is headed. Understanding how this technology can be integrated into pancreatic cancer care may help expand treatment options for patients with otherwise limited therapeutic choices.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to late presentation, limited resectability, therapeutic resistance, and a dense desmoplastic immunosuppressive tumor microenvironment that impairs drug penetration and antitumor immunity. Focused ultrasound (FUS) is an emerging non-invasive, image-guided therapeutic platform capable of delivering spatially confined acoustic energy to induce tumor ablation, disrupt stromal barriers, and enhance delivery of drugs, nanoparticles, and nucleic acids. Depending on acoustic parameters, FUS can produce thermal effects resulting in coagulative necrosis or non-thermal mechanical effects, including cavitation, sonoporation, and histotripsy which remodel extracellular matrix architecture, increase vascular and cellular permeability, and facilitate tumor debulking. In addition, FUS-induced cell injury can promote immunogenic cell death and release tumor-associated antigens and danger signals, providing a rationale for combination strategies with chemotherapy, radiation, and immunotherapy. This review synthesizes the mechanistic foundations, preclinical modeling advances, and emerging clinical applications of FUS in PDAC, with emphasis on treatment integration, patient selection, real-time monitoring, and acoustic parameter optimization, while acknowledging current safety considerations and limited clinical toxicity data. Key limitations, translational challenges, and priority knowledge gaps are also discussed to define the role of FUS in multimodal PDAC care.