Abstract
New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely non-invasive, non-thermal, and non-ionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image-guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant pre-clinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.
Highlights
Histotripsy is a focused ultrasound ablation method that destroys tissue through the precise control of acoustic cavitation [1,2,3,4]
We provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports from a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients
A wide variety of subcutaneous and orthotopic tumor models have been established in mice, the majority of histotripsy studies, including the example histotripsy treatments shown in this study have focused on subcutaneous tumor injection models that allow straightforward assessments of tumor progression and treatment with minimal concerns regarding acoustic windows
Summary
Histotripsy is a focused ultrasound ablation method that destroys tissue through the precise control of acoustic cavitation [1,2,3,4]. Histotripsy has shown the ability to ablate tissue near vital structures such as major vessels, bile ducts, and nerves while preserving these structures [1, 3, 9, 13, 14]. Due to these features, histotripsy is currently being developed for multiple clinical applications, most notably for the treatment of cancer [1, 3, 4, 15].
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