Abstract
Paclitaxel exemplifies one of the key taxanes (paclitaxel, docetaxel, cabazitaxel), a group of versatile and effective drugs commonly used in chemotherapy for several major cancer types. These drugs work by stabilizing cellular microtubules, a unique mechanism to account for their impressive success in oncology. Unfortunately, side effects and inevitable development of resistance limit their utility. Hair loss (alopecia) is a well-known adverse side effect and poses a significant quality of life issue for many patients. Substantial efforts have been made to prevent or limit alopecia in chemotherapy, however their efficacy is minimal.
We discovered that a brief exposure to low intensity and low frequency ultrasound at a defined timing is able to eliminate toxicity of paclitaxel (and other taxanes) in cultured cells by breaking the stabilized cellular microtubules. We subsequently showed that a brief exposure of low intensity ultrasound was able to break cellular microtubules and mitotic spindles transiently in hair follicle matrix cells of the furred skin of live mice. Such treatment reversed mitotic arrest by paclitaxel in the proliferative hair follicle matrix cells and prevented cell death, and thus annulled the consequent hair follicle damage and suppression of hair growth following paclitaxel administrations. These experimental findings herald a practical method that is within reach to prevent hair loss in cancer chemotherapy using taxanes.