FILLERON , Thomas

Variations in clinical response to tamoxifen (TAM) may be related to polymorphic cytochromes P450 (CYPs) involved in forming its active metabolite endoxifen (ENDO). We developed a population pharmacokinetic (PopPK) model for tamoxifen and six metabolites to determine clinically relevant factors of ENDO exposure. Concentration‐time data for TAM...

In addition to the effect of cytochrome P450 ( CYP ) 2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy and toxicity). This analysis focused on the pharmacokinetic (PK)‐pharmacogenetic evaluation of tamoxifen in 730 patients with adjuvant breast...

Over the last decades, molecular signatures have become increasingly important in oncology and are opening up a new area of personalized medicine. Nevertheless, biological relevance and statistical tools necessary for the development of these signatures have been called into question in the literature. Here, we investigate six typical selection...

Resistance mechanisms to immune checkpoint inhibitors (ICI) in cancer patients are not fully understood and predictive biomarkers are lacking. TNF is a pleiotropic cytokine that can be detrimental in cancer and TNF blockade potentiates ICI efficacy in preclinical models. MELANFα (NCT03348891) is a translational proof-of-concept, open-label,...

BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAF V600Emutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that...

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the...

Abstract Immune checkpoint inhibitors (ICIs) have dramatically modified the prognosis of several advanced cancers, however many patients still do not respond to treatment. Optimal results might be obtained by targeting cancer cell metabolism to modulate the immunosuppressive tumor microenvironment. Here, we identify sphingosine kinase-1 (SK1)...