From HAMLET to XAMLET: The molecular complex selectively induces cancer cell death

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex consisting of decalcinated alpha-lactalbumin and oleic acid. It has been shown to induce massive cell death in various cancers without serious damage to normal tissues in both in vitro and in vivo experiments. The complexity of the mechanism in the cellular functions of HAMLET results from its heterogeneous compositions as revealed from the structural analyses, as well as its induction of the non-canonical cell responses different from the specific classical programmed cell death. As the remarkable progress was made in the studies of HAMLET in recent years, a variety of HAMLET-like substances have been demonstrated to exert similar biological activities to HAMLET. Here, we termed these species as the XAMLET, and overviewed the current findings in XAMLET studies for a better understanding of their functions and working mechanisms. This review might contribute to the improvement in the application of XAMLET towards clinical cancer therapies.