The roles of ATP-binding cassette transporter A1 and its substrate cholesterol in head and neck cancers.

Head and neck cancer (HNC), which is among the deadliest malignancies, is the seventh most common cancer worldwide. How cholesterol homeostasis is linked to human cancers has long been a source of curiosity. One of the few proteins that are involved in cholesterol homeostasis is ATP-binding cassette transporter A1 (ABCA1), which is broadly expressed in numerous tissues. ABCA1 increases cholesterol efflux, inhibits cholesterol deposition in cells, and modulates anticancer activities. Therefore, it is not surprising that decreased ABCA1 activity and altered cholesterol homeostasis are implicated in the patho-physiology of HNCs. In this review, we focus on the role of cholesterol metabolism in the patho-physiology and progression of HNCs, with an emphasis on biological effects of ABCA1 transporters. We also review therapeutic approaches targeting cholesterol metabolism, as well as how combining such approaches with existing anticancer treatments may have synergistic effects and therefore open up new therapeutic avenues.