A translational systems medicine approach to provide predictive capacity for DTIC-based chemotherapy responsiveness in metastatic malignant melanoma

During the past three decades, melanoma incidence has increased approximately five fold in Ireland and the UK, despite extensive risk-awareness and prevention campaigns. Worryingly, melanoma chemotherapies have not improved during this time period nor have reliable markers been identified which would enable the identification of individual patients that will respond to the current standard chemotherapeutic, dacarbazine (DTIC). Our group aim to rectify this situation and develop markers that can predict outcome to this drug. For this we have developed a novel systems biology approach that combines cell biology, statistics, pattern recognition and machine learning. This novel technology allows us to predict the response of skin cancer cells in laboratory conditions to DTIC chemotherapy. In this current project, we will validate this approach in a clinically relevant setting by analysing patient tumour tissue samples and their responsiveness to therapy. We will also further develop our technology to gain predictive capacity for DITC in combination with novel drugs e.g. inhibitors of specific kinase proteins. Such combination treatments are currently being investigated in clinical trials for melanoma patients and hence may become future treatment options. Our project therefore holds tremendous potential to develop a clinically relevant tool that can identify patients that will likely benefit from currently approved and novel treatment options. We have formed a multi-disciplinary research team, including systems biologists, translational cancer researchers and clinician collaborators, to execute our proposal and validate our novel systems biology technology in clinical practice. The aims of this research address one of the most significant problems in the field of skin cancer, and we are confident that our research can make a significant contribution towards improving melanoma treatment and patient survival in the future.

This project is funded by HRB.