Ultrasound as a cancer chemotherapy sensitizer: the gap between laboratory and bedside

Introduction: The use of ultrasound to sensitize chemotherapy has been explored, a large amount of encouraging preclinical data has been reported, and an increase in drug influx is considered the main mechanism, leading scientists to believe that ultrasonic chemotherapy will change clinical practice.Areas covered: Here we first outline the clinical efficacy of ultrasonic chemotherapy using data from controlled trials of high-intensity focused ultrasound (HIFU)-chemotherapy, and then discuss the gap between laboratory and bedside. Data from clinical trials showed that focused ultrasound enhanced anticancer drugs in only 35.0% (7/20) of trials. Preclinical trials indicate that ultrasound augments the action of drugs via multiple pathways. The effect of a transient increase in the intracellular drug level due to ultrasound can be counteracted by certain cellular factors, causing a lack of chemosensitization. The experimental method used can lead to biases in preclinical trials.Expert opinion: Chemotherapy should not be recommended in HIFU treatments at present. The use of HIFU-chemotherapy in digestive-tract cancers can provide feedback for preclinical and translational researches in ultrasonic chemotherapy. The clinical relevance of preclinical trials should be improved; the drug-ultrasound interactions, sequence effects, predictiveness of in vivo models, and adjuncts of ultrasonic sensitization should be particularly considered.