|Isabelle VILGRAIN |
|Odile FILHOL |
During cancer progression, deregulated cell invasion contribute to metastatic dissemination. Cell invasion relies on the interactions between several cell types and cross-talks between signaling pathways. The emerging technologies of 3D cell cultures are developed for these cell signaling studies and for anti-metastatic drug screening.
ACTIVITES DE RECHERCHE / SERVICES
The incidence and associated mortality of kidney cancer has increased in recent years. Despite earlier detection, patients develop metastases or become resistant to current treatments that are short-acting. For this reason, new therapeutic molecules are currently being researched very actively. We have recently identified by a chemo-genomic library screening approach a new combination of molecules targeting CK2 and ATM protein kinases whose inhibition is particularly effective in inducing cancerous kidney cell death. In a preclinical study called COMBOREIN, our goal now is to test our molecules directly on tissue cultures derived from tumors of the patient’s kidney.
COMPETENCES / MOYENS TECHNIQUES
We have developped different 3D cultures models of ccRCC emphazing the feasibility and the advantage of human ccRCC tissue slice culture as a preclinical model. We have generated 786-O spheroids that are treated with a panel of drugs. Dead cell quantification is recorded using an Incucyte microscope. We also used tissue slice culture from ccRCC PDX mice or fresh human renal carcinoma tissue (Urology department, CHU-Grenoble-Alpes) that are cultured in presence of drugs for 2 days. Slice tissue cultures are processed for fluorescent live and dead testing and immuhistochemistry analysis. This approach is feasible, thanks’ to a preclinical Trail COMBOREIN (NCT03571438).
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IRIG, CEA Grenoble
U1036 INSERM UMR 1036 (BCI Biology of Cancer and Infection)
17 rue des Martyrs 38054