HAMLET – A protein-lipid complex with broad tumoricidal activity

James C S Ho, Aftab Nadeem, Catharina Svanborg

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)454-458
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume482
Issue number3
DOIs
Publication statusPublished - 2017 Jan 15

Subject classification (UKÄ)

  • Cell and Molecular Biology
  • Cancer and Oncology

Free keywords

  • Cancer
  • Cell death
  • HAMLET
  • Ion flux
  • Membrane
  • Oncogene

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