Conferences
2015
Conférence GIRC
Grenoble Institute for Cancer Research
.
Tuesday 1 December
Odile Filhol-Cochet
CEA, Grenoble
IAB Conference room 11 am
COMBINATION THERAPY TARGETING THE
CK2 AND ATM KINASES DEMONSTRATES
SYNERGISTIC THERAPEUTIC EFFICACY IN
KIDNEY CANCER
In 2011, about 11090 new cases of kidney cancer occurred in France making it the 10th most
common cancer. The most frequent type of Kidney cancer is Clear Cell Renal Cell Carcinoma
(CCRCC). Because RCC has mild or no symptoms, between 25-30% of the patients will
develop metastatic renal cell carcinoma (mRCC) by the time they are diagnosed. Metastatic
RCC has a poor prognosis compared to other cancers. RCC is notably highly resistant to
chemotherapy. However, over the past years, kinase-targeted therapies have become the
mainstay of treatment for mRCC. These new drugs target cellular protein kinases including
the tyrosine kinase receptors VEGFR and PDGFR (p.e Sunitinib, Sorafenib) and the mTOR
kinase (mTOR) (Temsirolimus). However most, if not all, patients acquire resistance to these
approaches over time after a median of 6–15 months of treatment.
To identify novel therapeutic targets we have performed a chemo–genomic High Throughput
Screening looking for efficient drug combinations against CCRCC. Over more than 5000
tested combinations, a very interesting hit came out that targets ATM and CK2 protein
kinases. We are now evaluating the efficacy of this drug combination both in 2D and 3D cell
culture models. Multi Cellular Tumor Spheroid (MCTS) is a 3D model where the
organization of a micro-tumor is reproduced, recapitulating cell-cell and cellmicroenvironment interactions. Using different 3D cultures such as MTCS and Tissue Slide
culture techniques we showed that this never described drug combination could be a novel
alternative therapy against metastatic renal cell carcinoma. Thus our work offers a strong
rationale to combine CK2 and ATM inhibitors in clinical trials.
Invited by Karin Sadoul
Grenoble Institut Recherche Cancer : Institut Albert Bonniot, Institut de Recherches en
Technologies et Sciences pour le
Vivant, Institut de Biologie Structurale, Grenoble Institut Neurosciences
Rond Point de La Chantourne, 38700 La Tronche (tram line B, stop: Grand Sablon)
The seminar is followed by discussions and exchanges with the speaker and a sandwich buffet is offered.
http://www-iab.ujf-grenoble.fr