Poster Presentation 31st Lorne Cancer Conference 2019

Developing targeted drug delivery for the treatment of melanoma (#347)

Amy Oxlade 1 , Rasika Samarasinghe 1 , Sarah Shigdar 1 2
  1. School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia
  2. Centre for Molecular and Medical Research, Deakin University , Waurn Ponds, Victoria, Australia

Melanoma is considered a dangerous cancer due to its likelihood to metastasize, with approximately 40% of patients developing metastases to distant organs, especially the brain. With a mean survival time of 9.2 months and a 5-year survival rate of 5-19% after the onset of distant metastasis, the prognosis for metastatic melanoma patients is very poor. Conventional therapies, such as chemotherapy and radiotherapy, are very toxic to patients due to their off-target effects, and generally cannot eradicate tumours due to a build-up of resistance to the treatments. Major breakthroughs in melanoma treatment occurred with the development of immunotherapy and antibodies such as ipilimumab and nivolumab. However, clinical studies showed that antibodies are limited due to their high immunogenicity, large size and lack of tissue penetration. Alternatively, other agents such as nanoparticles and aptamers may provide alternative methods for directed drug delivery with minimum off target effect. Aptamers, also known as chemical antibodies, are a novel therapy that binds to targets with high specificity and affinity. Aptamer-mediated drug delivery allows for a superior concentration of drug to be delivered to target cells, reducing off-target effects, overcoming drug resistance, and reducing the dose administered to patients. One of the key factors that warrant specific delivery of drug carriers to diseased tissues is determining the surface characteristic of cells and the molecules expressed. The first aim of this research is to investigate suitable putative biomarkers highly expressed on primary and metastatic melanoma cells. Following the identification of a protein target, aptamers will be generated against the selected protein with further truncations and characterizations made for high binding affinity with a minimal number of nucleotides in the aptamers binding region. Following aptamer generation, aptamer-drug conjugates will be developed and tested for enhanced uptake of cytotoxic drugs to melanoma cells. In the future, the use of aptamers as targeted drug delivery agents has the potential to improve survival rates and quality of life.