Ultrasound-Stimulated Microbubbles in Cancer Therapy: A Review of Clinical and Translational Evidence

Abstract Ultrasound-stimulated microbubbles (USMB) have evolved from a diagnostic contrast technology into an investigational cancer therapy. Acoustically driven microbubble cavitation generates localized mechanical effects that can permeabilize cell membranes, disrupt tumor vasculature, and transiently open biological barriers. This review synthesizes the clinical and translational evidence for USMB-based oncologic therapy across its three principal applications: radiosensitization, drug delivery, and thermal ablation. A narrative review of English-language literature was conducted using PubMed/MEDLINE through April 2026. Radiosensitization is most clinically advanced in liver malignancies, supported by phase 2 randomized data in hepatocellular carcinoma and an efficacy signal in intrahepatic cholangiocarcinoma, with early-phase trials in breast and head and neck cancer. USMB-enhanced drug delivery is most developed in glioma, where implantable and noninvasive focused-ultrasound systems for blood–brain barrier opening have shown feasibility, pharmacokinetic enhancement, and a recent overall-survival benefit; pancreatic cancer provides the strongest randomized evidence outside the brain and liver. Thermal-ablation enhancement remains predominantly preclinical. USMB shows growing clinical promise across multiple tumor types, but the evidence base is constrained by small, heterogeneous trials, the absence of completed phase 3 studies, and off-label agent use. Standardized protocols and larger randomized trials are needed before routine clinical adoption.