High-Intensity Focused Ultrasound Applications in Cancer Therapy

High-intensity focused ultrasound (HIFU) harnesses convergent acoustic energy to generate precise thermal and mechanical effects within tumours, offering a non-invasive alternative to surgery or radiotherapy. By focussing ultrasound beams onto millimetre-sized targets, HIFU induces coagulative necrosis through rapid temperature elevation or tissue fractionation via cavitation. Thermal HIFU has been employed in the treatment of solid malignancies—including liver, prostate, breast and pancreatic tumours—under real-time magnetic resonance or ultrasound guidance to ensure accurate ablation margins and minimise collateral damage. More recently, non-thermal modalities such as histotripsy have emerged, using high-amplitude, short-pulsed exposures to mechanically disintegrate tissue without significant heat deposition. These mechanical approaches not only achieve local tumour control but also release intact antigenic proteins and damage-associated molecular patterns, thereby potentiating systemic immune activation. Integration with nanomaterials, microbubbles or immunomodulatory agents further enhances tumour selectivity, drug delivery and antitumour immunity. Collectively, HIFU technologies are advancing towards personalised cancer therapy by combining precise tumour eradication with immunological and pharmacological synergies, underscoring their growing global significance and translational potential.

Research from Nature Portfolio

Recent studies have shown that boiling histotripsy can mechanically fractionate solid tumours, such as breast adenocarcinoma, without significant thermal damage. This mechanical ablation releases damage-associated molecular patterns (including CRT, HSP70 and HMGB1), which in turn promote immunogenic cell death via necrosis signalling pathways. The resulting cytokine and chemokine milieu enhances M1 macrophage activation and may potentiate systemic antitumour immunity. These insights underscore the potential of boiling histotripsy as both an ablation and immunomodulatory strategy in cancer therapy.

High-Intensity Focused Ultrasound Applications in Cancer Therapy publication trend

The graph below shows the total number of articles in high-intensity focused ultrasound applications in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

High-Intensity Focused Ultrasound (HIFU): A non-invasive modality that concentrates acoustic energy to ablate or mechanically disrupt target tissues.

Histotripsy: A mechanical HIFU technique using high-amplitude, short-pulsed ultrasound to induce cavitation and fractionate tissue without thermal damage.

Abscopal effect: Regression of distant, untreated tumours following local therapy, mediated by systemic immune mechanisms.

Damage-Associated Molecular Patterns (DAMPs): Endogenous molecules released from injured cells that activate innate immune receptors.

Conventional Dendritic Cells (cDC1 and cDC2): Professional antigen-presenting cells specialised in cross-presentation to CD8+ T cells (cDC1) and CD4+ T cells (cDC2).

Antigen Cross-Presentation: The process by which extracellular antigens are presented on MHC class I molecules to prime cytotoxic T lymphocytes.

References

1. An Introduction to High Intensity Focused Ultrasound: Systematic Review on Principles, Devices, and Clinical Applications. Journal of Clinical Medicine (2020).
2. MR‐guided focused ultrasound surgery, present and future. Medical Physics (2013).
3. Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound. International Journal of Hyperthermia (2021).
4. Boiling Histotripsy-induced Partial Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers. Scientific Reports (2019).
5. Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation. Theranostics (2013).
6. Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response. Journal of Translational Medicine (2012).
7. Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation. Theranostics (2018).
8. Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation. Theranostics (2024).
9. First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study. International Journal of Hyperthermia (2022).