The conference “Search, validation and clinical translation of new therapeutic targets in Ewing sarcoma found by integrative genomic analyses” by Enrique de Álava, researcher at the Cancer Research Centre (CIC), at the Hospital University of Salamanca and the Spanish High Research Council (CSIC), takes place last 9th November in IDIBELL.
“To try to translate into the clinics, I want to introduce the genesis of this particular tumour. There is a morphologic heterogeneity in Ewing sarcoma”, said de Álava. In Ewing sarcoma (EWS), the researchers use genetics and morphological analyses. There is a key molecular event, like gene fusions, mutations or copy of alterations, which act on the cell origins together with additional mutations.
There are some EWS-FLI1 targets and some factors that affect its activity. “We need some mutations or epigenetic alterations to explain the EWS episodes, like the p53 mutation or p16/p14ARF. We saw the functional relevance of the candidate gene CDT2”, said the researcher.
The microenvironment and the immune system are also very important in Ewing sarcoma. There is a tumour cellular hierarchy. The researchers need more molecular understanding in EWS. They find different problems: there is not preneoplastic lesion, not “normal tissue” counterpart and not a genetically modified animal model available. There is a not gut sample availability and there are too many markers, many of them are not enzymes.
“EWS-FLI1 is a good target”, admitted the researcher. “We can use a synergetic drug combination: two therapeutic targets in Phase I-II clinical trials in patients not responding to GEIS21”, concluded the researcher.