Ultrasound-mediated mechanical forces selectively kill tumor cells

Abstract Ultrasound has been used to target tumors either through local heating or local nanobubbles but these methods damage surrounding normal cells in the target area. Recent studies show that tumor cells are susceptible to mechanical stresses and undergo calcium-dependent apoptosis under conditions that promote normal cell growth. Here we report that low-frequency ultrasound causes apoptosis of tumor cells by activating a calpain-dependent mitochondrial pathway that depends upon calcium entry through the mechanosensitive Piezo1 channels. This is a general property of all tumor cell lines tested so far irrespective of tissue origin. In animals, ultrasound irradiation causes tumor killing in the chick chorioallantoic membrane (CAM) model with relatively little damage to the chick embryos. Further, patient-derived pancreatic tumor organoids are killed by ultrasound treatment. Because low-level ultrasound causes apoptosis of tumor cells from many different tissues in different microenvironments, it may offer a safe non-invasive approach to augment tumor treatments.