Study of new multi-target directed compounds for the treatment of glioblastoma / Determinants of biological levels of PFAS (Perfluorinated acids) and their evolution in the INMA cohort

Study of new multi-target directed compounds for the treatment of glioblastoma

Glioblastoma is the most prevalent and malignant brain primary tumour. It is characterized by its marked heterogeneity and current therapy includes the maximum surgical removal of the lesion followed by radiation and temozolomide-based chemotherapy and bevacizumab in recurrent cases. However, these treatments display a reduced benefit and the median survival of patients is 15 months. The paradigm of personalized medicine postulates the effective eradication of cancer through: a) stratification of patients and b) selection of the most consistent therapeutic treatment based on the molecular understanding of each individual or subgroup. Moreover, there is cellular heterogeneity and glioma stem cells should be relevant targets.

The research group has developed and patented a novel therapeutic strategy in glioblastoma through the generation of 4 families of multitarget compounds (EP1641.1884) directed against the inhibition of different signaling pathways. From all the initial compounds, we have selected the most promising ones and predicted their potential as drugs using online available prediction tools, studied their effect in glioma stem cells and characterized their downstream targets. I will summarize all these results.

Determinants of biological levels of PFAS (Perfluorinated acids) and their evolution in the INMA cohort

Per- and polyfluoroalkyl substances, or PFAS, are persistent organic compounds that are present in many of the products that we use in our daily life. Due to their long half-life, they bioaccumulate in animal and human tissues and can cause deleterious effects in human health. They are considered endocrine disruptors, so different studies have focused on endocrine-related diseases or conditions. Nevertheless, epidemiological data are still scarce, and the gap is even larger regarding effects in sensitive populations such as pregnant women and children. Therefore, in the INMA Project (Infancia MedioAmbiente) we have quantified different PFAS during pregnancy and infancy in order to describe the changing PFAS exposure profiles. In addition, we have studied the factors that explain PFAS levels in different stages during infancy. The results indicate that some of the legacy PFAS has decreased with time, what could be due to the public health policies applied during the last years. However, we have also detected emergent PFAS in the most recent samples, what indicates that the exposure pattern is changing and that we are exposed to novel compounds that need to be studied. Regarding the factors associated with PFAS levels during childhood, pregnancy levels and breastfeeding were positively associated with PFAS in the early childhood, while at 8 years of age, no significant associations could be observed. These results highlight the need for human biomonitoring to understand the changes of PFAS exposure trends and to assess their effects on human health.