PROJECT: Uso del editado génico mediado por CRISPR para el estudio y tratamiento del cáncer de ovario de células de la granulosa.

PI: Ignacio Pérez de Castro Insúa.

PERIOD/AMOUNT: 2017-2018; 20.000€.

FUNDING AGENCY: AECC, Ideas Semilla 2017

PROJECT: Uso de terapias avanzadas para el tratamiento del cáncer de ovario de células de la granulosa.

PI: Jesús García-Donas.

PERIOD/AMOUNT: 2017-2018; 30.000€.

FUNDING AGENCY: Fundación Merk Salud, Ayudas Merk de Investigación 2017.

Orphan tumors constitute almost 25% of all the human cancers. Due to their low incidence, these cancers are poorly understand and few effective treatments have been discovered to fight against them. In collaboration with Dr. Jesus García Donas, at the Clara Campal Cancer Comprehensive Center, we have initiated a research line focused on the study of rare cancers. Specifically, we will establish cellular models (2D and 3D) from biopsies and use them for a better characterization of the disease and the search of new therapeutic opportunities.

We have initiated this collaborative work with the generation of two cancer cell lines from two renal cancers carrying SDHB and FLCN mutations and with the study of granulosa cell ovarian cancers. For the latter, a tumor type characterized for the presence of a unique mutation in the transcription factor FOXL2, our objectives are:

(1) Study of the role of FOXL2 in the granulosa cell tumorigenesis

by (i) the generation and characterization of 3D cultures from granulosa cell tumors carrying the mutation FOXL2_402G>C, (ii) the generation and characterization of an experimental mouse model (FOXL2_402G>C) and (iii) studying the effect of genetic reversion, mediated by CRISPR/Cas9, of the mutation FOXL2_402G>C into a wild-type status.

(2) Search of efficient therapeutic strategies for the treatment of the granulosa cell tumors of the ovary

by (i) exploring the use of inhibitors of the steroid biosynthesis pathway; (ii) the search for compounds, already approved by the FDA