OPTIMTA focuses on mathematical/statistical modelling-based personalized medicine to enable patients receive the best drug therapy. Given that the stress response has been implicated in multiple diseases, including in melanoma patients that are subject to immunotherapy, it is important to determine if endoplasmic reticulum (ER) stress markers can be used as predictive markers of disease development and treatment response.
Multidisciplinary and Intersectoral Approach: assessing the unfolded protein response (UPR) for predictive value in melanoma patients (A project for a PhD student - ESR14). ESR14 will deep sequence and quantitate ER stress-related factors in tumour tissue samples taken from a cohort of 100 melanoma patients who were treated with Pembrolizumab (Keytruda) or Ipilimumab (Yervoy). Subsequently, ESR14 will use the OPTIMATA high level multiscale modelling platform to determine the value of these markers for predicting response to immunotherapy prior to treatment. ESR14 will isolate DNA and RNA from patient samples and, on 1-year secondment, will utilize National University of Ireland, Galway (NUIG)’s expertise in RT-PCR and their primers to measure the transcript levels of approximately 100 UPR ER stress-related factors.
· Deep sequencing of the genomic regions of these ER stress-related factors will also be performed and will identify mutations and SNPs.
· ESR14 will incorporate these data with the associated patient medical and treatment data into OPTI modelling systems to determine which ER stress-related factors have predictive value in melanoma.
· If factors with predictive value are identified their value in other types of cancer could be rapidly assessed.