Beta-hairpin peptides as therapeutics to treat drug-resistant metastatic melanoma

Dr Sónia T. Henriques, Senior Lecturer/Group Leader
Institute of Health and Biomedical Innovation and Translational Research Institute
School of Biomedical Sciences, Queensland University of Technology (QUT), presents: 

Beta-hairpin peptides as therapeutics to treat drug-resistant metastatic melanoma

Acquired drug resistance is a serious problem for the treatment of metastatic melanoma. Current treatments have low specificity, high toxicity toward healthy cells, and induce drug-resistance. We have designed cyclic peptides inspired on host defense peptides with a Beta-hairpin structure that selectively target and kill melanoma cells, including those harbouring BRAF V600E mutation. These peptides are resistant to proteases, can cross cell membranes, and are amenable to structural modifications.

We have identified peptide analogues able to kill drug-sensitive and drug-resistant metastatic melanoma cells that have developed resistance to Dabrafenib, a small molecule drug used to treat patients with metastatic melanoma with BRAF V600E mutation. In addition, metastatic melanoma cells did not develop tolerance to tested peptides. Thus, these host defense peptides are well suited as templates to design therapeutic leads to target drug-resistant metastatic melanoma cells and/or as co-treatment with small molecule drugs. I will present results on the activity and mechanism of these anti-melanoma peptides and on lipidomic studies of melanoma cell membranes.

- Dr Sónia T. Henriques

Bio: Dr Sónia Henriques researches peptides to treat cancer and infectious diseases. Her research group in Peptide Therapeutics and Membrane Biology focuses on characterizing cell membranes and in designing peptide therapeutics able to target unique cell membrane properties, cross cell membranes, and deliver drugs inside cancer/infectious cells. Dr Henriques graduated in Biochemistry (2003) and obtained a PhD degree in Biochemistry/Molecular Biophysics (2008) from the University of Lisbon in Portugal. She conducted postdoctoral research at the University of Queensland at the Institute for Molecular Bioscience (IMB) in Professor David Craik’s group, and at the University of Lisbon in Portugal in Professor Miguel Castanho’s group. She is the recipient of highly competitive fellowships (ARC Australian Postdoctoral Fellowship 2008; Marie Curie Fellowship 2009; ARC DECRA 2012; ARC Future Fellow 2015). She is a research group leader at the Translational Research Institute (TRI) and a senior lecturer in Biochemistry at Queensland University of Technology.

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