title: HAMLET - A protein-lipid complex with broad tumoricidal activity.
abstract: HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET internalization, progressive inhibition of MAPK kinases and GTPases and sorting of HAMLET to different cellular compartments, including the nuclei. Therapeutic efficacy of HAMLET has been demonstrated in animal models of glioblastoma, bladder cancer and intestinal cancer. In clinical studies, HAMLET has been shown to target skin papillomas and bladder cancers. The findings identify HAMLET as a new drug candidate with promising selectivity for cancer cells and a strong therapeutic potential.
authors.affiliation: Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, S-223 62 Lund, Sweden; Centre for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Drive, 637553, Singapore.
authors.forename: James C S
authors.initials: JCS
authors.lastname: Ho
authors.affiliation: Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, S-223 62 Lund, Sweden.
authors.forename: Aftab
authors.initials: A
authors.lastname: Nadeem
authors.affiliation: Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, S-223 62 Lund, Sweden. Electronic address: catharina.svanborg@med.lu.se.
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007768:Lactalbumin / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009829:Oleic Acids / Q000737:chemistry / Q000494:pharmacology*; D009857:Oncogenes; D061988:Proteasome Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; C506422:HAMLET complex, human; D009829:Oleic Acids; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors; D007768:Lactalbumin
keywords: Cancer; Cell death; HAMLET; Ion flux; Membrane; Oncogene