Ghanim 2017 MiPschool Obergurgl

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Magda Ghanim
HAMLET derivatives as a pre-operative therapy in oesophageal cancer.

Link: MitoEAGLE

Ghanim M, Mok K, Kelly VP (2017)

Event: MiPschool Obergurgl 2017

COST Action MitoEAGLE

Oral and oesophageal cancers are aggressive tumours associated with high morbidity and mortality. Lack of early detection strategies is one of the reasons for late diagnosis, since these cancers often do not exhibit any symptoms until entering advanced stages. Their pathogenesis is still unclear, thus there are few satisfactory therapies. Difficulties in operating on oral cavity or oesophagus, as well as applying radiotherapy and often occurring chemotherapy resistance in these cancers is a major set back in increasing the survival rate of the patients. Due to the unfortunate placement of the tumours, patients experience difficulties with swallowing, chewing, breathing and talking, during the disease as well as during the therapy. Surgeries often greatly lower the comfort of living of patients, leave scars and the overall survival rate still remains low. Development of an effective adjuvant therapeutic agent that would gently ease the symptoms and quickly reduce the size of the tumour before applying more invasive therapies could greatly increase the comfort of patients and ideally increase the survival rate.

HAMLET - Human Alpha-lactalbumin Made LEthal to Tumour cells – is a complex formed from partially unfolded α-lactalbumin and oleic acid. Discovered by Catharina Svanborg and her group while studying the anti-bacterial properties of human milk on human lung cancer cells, HAMLET has been since proven to selectively target tumour cells and causing their death while having no such effect on healthy differentiated cells. It is the first identified protein that has a defined function in its native site and acquires a new beneficial function after partial unfolding. Other similar protein-fatty acid complexes that exhibit similar cytotoxic properties have been since identified.

The project aims to decipher the cellular mechanism that makes HAMLET selectively toxic to cancer cells. In particular, the research will focus on the process of metabolic transformation including aerobic glycolysis, extracellular acidification and membrane hyperpolarisation. It is hoped that by identifying the critical characteristics that selectively kill cancer cells, that it will be possible to further enhance HAMLET’s efficacy as an adjuvant therapy.


Bioblast editor: Kandolf G


Labels: MiParea: Pharmacology;toxicology  Pathology: Cancer 







Affiliations

School Biochem Immunol, Trinity College Dublin, Ireland.- mghanim@tcd.ie

References

  1. Ho JC, Nadeem A, Svanborg C (2017) HAMLET – A protein-lipid complex with broad tumoricidal activity. Biochem Biophys Res Commun 482:454-8.
  2. Min S, Meehan J, Sullivan LM, Harte NP, Xie Y, Davey GP, Svanborg C, Brodkorb A, Mok KH (2012) Alternatively folded proteins with unexpected beneficial functions. Biochem Soc Trans 40:746-51.