Year of publication 2018
Involvement of the FOXO6 transcriptional factor in breast carcinogenesis.Oncotarget : 7464-7475 : DOI : 10.18632/oncotarget.23779 Learn more
In mammals, FOXO transcriptional factors form a family of four members (FOXO1, 3, 4, and 6) involved in the modulation proliferation, apoptosis, and carcinogenesis. The role of the FOXO family in breast cancer remains poorly elucidated. According to the cellular context and the stage of the disease, FOXOs can have opposite effects on carcinogenesis. To study the role of FOXOs in breast carcinogenesis in more detail, we examined their expression in normal tissues, breast cell lines, and a large series of breast tumours of human origin. We found a very low physiological level of expression in normal adult tissues and high levels of expression in foetal brain. gene expressions fluctuate specifically in breast cancer cells compared to normal cells, suggesting that these genes may have different roles in breast carcinogenesis. For the first time, we have shown that, among the various genes, only was frequently highly overexpressed in breast cell lines and tumours. We also found that inhibition of the endogenous expression of FOXO6 by a specific siRNA inhibited the growth of the human breast cell lines MDA-MB-468 and HCC-38. FACS and Western blot analysis showed that inhibition of endogenous expression of FOXO6 induced accumulation of cells in G0/G1 phase of the cell cycle, but not apoptosis. These results tend to demonstrate that the overexpression of the human gene that we highlighted in the breast tumors stimulates breast carcinogenesis by activating breast cancer cell proliferation.Fold up
Year of publication 2017
Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild-type metastatic colorectal carcinoma.British journal of cancer : 1819-1827 : DOI : 10.1038/bjc.2017.353 Learn more
Metastatic colorectal cancer (mCRC) patients with mutant KRAS or NRAS are ineligible for anti-epidermal growth factor receptor (anti-EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. However, even among RAS wild-type (WT) patients, only a fraction responds to anti-EGFR therapy, suggesting that other mechanisms of resistance exist. We hypothesise that different (epi)genetic alterations can lead to primary anti-EGFR resistance and that the crucial end point is the activation of protein signalling pathways.Fold up
IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer.BMC cancer : 636 : DOI : 10.1186/s12885-017-3618-5 Learn more
The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway – insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins (IGFBP1-7, IGF2BP1-3) – in bladder cancer and its correlation with IGF1R activation, and the anti-proliferative efficacy of an IGF1R kinase inhibitor in this setting.Fold up
Predictive biomarkers of resistance to hypofractionated radiotherapy in high grade gliomaRADIATION ONCOLOGY : 12 : 123 : DOI : 10.1186/s13014-017-0858-0 Learn more
Background: Radiotherapy plays a major role in the management of high grade glioma. However, the radioresistance of glioma cells limits its efficiency and drives recurrence inside the irradiated tumor volume leading to poor outcome for patients. Stereotactic hypofractionated radiotherapy is one option for recurrent high grade gliomas. Optimization of hypofractionated radiotherapy with new radiosensitizing agents requires the identification of robust druggable targets involved in radioresistance.
Methods: We generated 11 xenografted glioma models: 6 were derived from cell lines (1 WHO grade III and 5 grade IV) and 5 were patient derived xenografts (2 WHO grade III and 3 grade IV). Xenografts were treated by hypofractionated radiotherapy (6x5Gy). We searched for 89 biomarkers of radioresistance (39 total proteins, 26 phosphoproteins and 24 ratios of phosphoproteins on total proteins) using Reverse Phase Protein Array.
Results: Both type of xenografted models showed equivalent spectrum of sensitivity and profile of response to hypofractionated radiotherapy. We report that Phospho-EGFR/EGFR, Phospho-Chk1/Chk1 and VCP were associated to resistance to hypofractionated radiotherapy.
Conclusions: Several compounds targeting EGFR or CHK1 are already in clinical use and combining them with stereotactic hypofractionated radiotherapy for recurrent high grade gliomas might be of particular interest.Fold up