S100A9-dependent radiation resistance in brain metastasis
Worldwide Cancer Research
Spanish National Cancer Research Centre
With the advent of improved diagnosis and novel therapeutic approaches cancer patients live longer with systemic disease. However this increased survival is paradoxically associated with a growing incidence of brain relapses. Brain metastasis remains an unmet clinical need with limited therapeutic possibilities. Among them, brain irradiation has been applied for decades yet its efficacy to improve the course of the disease is controversial. Why radiation therapy does not yield better responses given its probed ability to penetrate the brain?. We want to perform in vivo experiments to test a biomarker of radiation resistance that we have discovered using a non-biased approach. This biomarker could be particularly important in situ. Consequnetly, our approach will use advanced models of brain metastasis from breast and lung cancer, including immunosuppressed models but also newly established immunecompetent ones and brain metastasis PDX. We present a research proposal by which, in collaboration with clinicians, we will be able to evaluate the translational potential of a biomarker to predict responses to radiation therapy, thus offering the possibility to personalized this therapeutic approach. In addition, to improve the efficacy of radiotherapy without inducing neurotoxicity, we will use a BBB-permeable drug that blocks the signaling pathway inducing therapeutic resistance downstream of the biomarker. Our proposal is based on strong preliminary data, leading expertise in brain metastasis research and experienced clinical collaborators that will allow us to make a significant contribution on the poorly defined biology of therapeutic resistance of brain metastasis.
5.1 Pharmaceuticals