HAMLET: Functional Properties and Therapeutic Potential

James Ho CS; Anna Rydström; Maria Trulsson; Johannes Bålfors; Petter Storm; Manoj Puthia; Aftab Nadeem; Catharina Svanborg


Future Oncol. 2012;8(10):1301-1313. 

In This Article

Future Perspective

To further elucidate the HAMLET phenomenon, a combination of structural studies, cell biology, animal models and clinical trials will be needed. It is encouraging that several international groups actively pursue this field of research.[12,42,45,46,55,75,92] New data on the structure of HAMLET, BAMLET, ELMLET and other similar complexes are rapidly being generated. Cellular targets that initiate the cell death process are being identified in the cytoplasmic membrane and it should be possible in the near future to characterize targets that distinguish tumor cells from healthy, differentiated cells in order to understand the relative tumor selectivity of HAMLET. Finally, the range of therapeutic targets for HAMLET is being expanded, hopefully serving as a source of inspiration for continued development of HAMLET into a fully available therapeutic agent.

Specifically, we propose that HAMLET should be further explored as a novel therapeutic agent against HPV-induced tumors. HPV infection is an important cause of cervical cancer,[93] making effects on skin papillomas of potential interest for patients with cervical dysplasia or HPV-induced genital warts. HPV vaccines are efficient new tools to prevent cervical papillomas, although the morbidity in unvaccinated subjects remains a major health issue. A study of topical HAMLET administration in women with cervical dysplasia would be of great interest, as removal of cervical tissue by conization remains the only therapeutic option at present.

We also propose that the therapeutic value of HAMLET should be explored in controlled trials of bladder cancer and brain tumors, where experimental and human data are available. Further characterization of basic mechanisms of cell death regulation may also be useful to design future disease therapies involving both eukaryotic and prokaryotic cells.