Few molecules destroy cancer cells without harming healthy tissues. While more targeted cancer therapies are starting to appear, the lack of specificity for tumor cells remains a significant problem. New concepts and innovative approaches are needed to achieve tumor specific cell death and to develop more tumor selective therapies.

HAMLET (Human α-lactalbumin Made LEthal to Tumor cells) is a complex of partially unfolded -lactalbumin and oleic acid that kills tumor cells and immature cells but not fully differentiated healthy cells. We discovered HAMLET by serendipity, in a fraction of human milk that killed lung carcinoma cells and characterized the constituents of the complex. Early in vitro experiments showed that HAMLET has broad anti-tumor activity with a high degree of selectivity.

HAMLET is the first member in a new, expanding family of unfolded protein-lipid complexes that kill a broad range of cancer cells, while sparing normal, differentiated cells. HAMLET thus identifies targets that are highly conserved among cancer cells and whose activation tilts the balance from exaggerated survival to death. This application concerns the structure, cellular targets and in vivo effects of HAMLET. This work is particularly significant in view of HAMLET’s already documented therapeutic effects in patients and animal models.