When surgery, radiotherapy, and chemotherapy fail to treat metastatic melanoma, immunotherapy has been shown to be the best option, boosting our body’s natural defenses to eliminate cancer cells. However, several melanoma patients develop mechanisms of resistance to this treatment. Our research is focused on discovering these mechanisms, and engineering new strategies to overcome resistance to current immunotherapies.
Using new data mining approaches, we are able to visualize the most important genes that are hiding cancer cells from the immune system of melanoma patients that do not respond to immunotherapies.
Tumor cells are genetically unstable, meaning that they are constantly changing their genome, a fact well-known to make them randomly weak or strong at the same time. When treatments come along, weak cancer cells will die, but strong ones will adapt and resist the treatments. This is all given to the genetic evolution of these cells. We want to reverse the genetic evolution of melanoma cells by treating them with specific drugs previously predicted to do so in an in silico environment.
By designing a completely new immune phenotyping single-cell antibody panel in a state-of-the-art approach, we are not only profiling the systemic immune response of refractory melanoma patients but also investigating for the first time the expression levels of functional proteins related to the immune genes discovered in Project 1.
We already found valuable biomarkers that impact patients’ survival and response to immunotherapies. Using pre-clinical approaches, we are testing approved drugs as agonists and antagonists for these biomarkers in combination with current immunotherapies so that they can be quickly validated as repurposed drugs in clinical trials.