Using ultrasound and microbubble to enhance the effects of conventional cancer therapies in clinical settings

It has been demonstrated in preclinical research that the administration of microbubbles with ultrasound can augment the proapoptotic sphingolipid pathway and enhance chemotherapy or radiation therapy-induced vascular endothelial disruption resulting in enhanced tumor cell death. Specifically, ultrasound-stimulated microbubbles (USMB) can increase blood vessel permeability facilitating the release of therapeutic substances in the target area. USMB can also serve as a potential radiation enhancing therapy as USMB exposure increases tumor cell death significantly as observed in preclinical models. Clinical studies have found the combination of USMB and these existing cancer therapies to be safe and also to be associated with greater tumor responses. USMB-based treatment can be applicable in a clinical setting using either ultrasound imaging or magnetic resonance imaging (MRI) guidance for precise treatment. In the latter, the ultrasound device is integrated into the MRI system platform for sonication to facilitate microbubble stimulation. In this review, we concisely present findings related to USMB and existing cancer therapies (chemotherapy and radiation therapy) in clinical trial settings. The possible underlying mechanism involved in USMB-enhanced chemotherapy or radiotherapy enhancement is also discussed. Lastly, the study concludes with some limitations and an examination of the future direction of these combined therapies.