A5017101736- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- Cancer Treatment and Pharmacology
- Breast Cancer Treatment Studies
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- Receptor Mechanisms and Signaling
- PI3K/AKT/mTOR signaling in cancer
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Colorectal Cancer Treatments and Studies
- Peptidase Inhibition and Analysis
- Olfactory and Sensory Function Studies
- Pharmacological Effects and Assays
- Advanced biosensing and bioanalysis techniques
- Metastasis and carcinoma case studies
- Insect Pheromone Research and Control
- Phosphodiesterase function and regulation
- Chronic Lymphocytic Leukemia Research
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
Institut Curie
2018-2025
Université Paris Sciences et Lettres
2018-2025
Translational Research in Oncology
2020-2023
Oniris
2014-2016
Université Nantes Angers Le Mans
2014-2016
Triple-negative breast cancer xenografts with BRCAness, high expression of SLFN11, and RB1 loss are highly sensitive to topoisomerase I inhibitors.
A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse metastatic disease. Here we perform whole exome sequencing gene expression analysis matched primary tumours bone metastasis-derived patient-derived xenografts (PDX). Transcriptomic analyses reveal enrichment the G2/M checkpoint up-regulation Polo-like kinase 1 (PLK1) in PDX. PLK1 inhibition results tumour shrinkage highly proliferating...
Abstract Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show model systems that other than loss RB1 few gene-copy number (CN) alterations are associated with irreversible-resistance to subsequent secondary resistance palbociclib. Resistance palbociclib occurred as a result tumour cell re-wiring leading increased expression EGFR, MAPK, CDK4, CDK2, CDK7, CCNE1...
Abstract Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic metabolomics analyses of patients’ tumours, metastasis-derived patient-derived xenografts (PDX) isogenic cell lines we demonstrate that fraction metastatic ER BC highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth multiple...
Abstract Oral selective estrogen receptor degraders (SERD) could become the backbone of endocrine therapy (ET) for receptor–positive (ER+) breast cancer, as they achieve greater inhibition ER-driven cancers than current ETs and overcome key resistance mechanisms. In this study, we evaluated preclinical pharmacology efficacy next-generation oral SERD camizestrant (AZD9833) assessed ER–co-targeting strategies by combining with CDK4/6 inhibitors (CDK4/6i) PI3K/AKT/mTOR-targeted in models...
Abstract The high frequency of homologous recombination deficiency (HRD) is the main rationale testing platinum-based chemotherapy in triple-negative breast cancer (TNBC), however, existing methods to identify HRD are controversial and there a medical need for predictive biomarkers. We assess vivo response platinum agents 55 patient-derived xenografts (PDX) TNBC determinants response. status, determined from whole genome sequencing, highly BRCA1 promoter methylation not associated with...
Purpose: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from tumors to identify efficient chemotherapies and predictive biomarkers in context of resistance anthracyclines- taxanes-based treatments.Experimental Design: PDX were established primary treated setting. TNBC by anthracyclines, taxanes, platins, capecitabine. Predictive identified transcriptomic immunohistologic...
Abstract Purpose: Here, we investigated the clinical relevance of an unprecedented combination three biomarkers in triple-negative breast cancer (TNBC), both human samples and patient-derived xenografts TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), retinoblastoma protein (RB). Experimental Design: IHC analyses were conducted on PDX-TNBC to evaluate production biomarkers. The sensitivity cells expressing or not MT4-MMP anti-EGFR (erlotinib) anti-CDK4/6 inhibitor...
Triple‐negative breast cancer (TNBC) represents 10% of all cancers and is a very heterogeneous disease. Globally, women with TNBC have poor prognosis, the development effective targeted therapies remains real challenge. Patient‐derived xenografts (PDX) are clinically relevant models that emerged as important tools for analysis drug activity predictive biomarker discovery. The purpose this work was to analyze molecular heterogeneity large panel PDX ( n = 61) in order test identify biomarkers...
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Abstract Background Metaplastic breast cancer (MBC) is a rare form of characterized by an aggressive clinical presentation, with poor response to standard chemotherapy. MBCs are typically triple-negative cancers (TNBCs), frequently alterations genes the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective this study was determine PI3K MAPK pathway inhibitors in patient-derived xenografts (PDXs) targetable alterations. Methods We compared survival between other histological subtypes,...
Breast cancer is the most common amongst women worldwide, however clinically validated chemotherapy response biomarkers that can accurately predict treatment in patients are largely lacking. Therefore, this study, functional paclitaxel and eribulin ex vivo sensitivity assays were developed. Patient derived xenograft (PDX) models used to compare predicted outcome with of mice vivo. We previously developed assay for paclitaxel, which based on ratio between replicating (EdU) mitotic...
Acquisition of resistance to anti-cancer therapies is a multistep process, which initiates with the survival drug persister cells. Understanding mechanisms driving emergence cells remains challenging, primarily because their limited accessibility in patients. Here, using mouse models isolate from patient tumors, we determine identity features eight patients triple-negative breast cancer (TNBC). Combining over 80 transcriptome studies, reveal hallmarks state across and treatment modalities:...
Abstract Background: Antibody-drug conjugates (ADCs) have emerged as highly effective new therapeutics for metastatic breast cancer (mBC). Sacituzumab govitecan (SG), an anti-TROP2 ADC, has been approved the treatment of ER+/HER2- and triple negative mBC trastuzumab deruxtecan (T-DXd), anti-HER2 HER2-amplified HER2-low mBC. Despite significant improvement in patients’ survival, several hurdles remain to overcome, including development predictive biomarkers optimal sequential strategy. The...
Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is to cell, have been successfully exploited treat cancer. GATA3 frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset patients with poor response hormonal therapy prognosis. However, yet targetable. Here we show that MDM2 are synthetically ER-positive Depletion pharmacological inhibition significantly impaired tumor growth GATA3-deficient...
Triple negative breast cancers (TNBCs) represent 15-20% of all and are associated with higher recurrence distant metastasis rate. Standard care for early stage TNBC is anthracyclines combined cyclophosphamide (AC) followed by taxanes, in the neo-adjuvant or adjuvant setting. This work aimed to identify predictive biomarkers AC response patient-derived xenograft (PDX) models validate them clinical By gene protein expression analysis 39 PDX different responses AC, we found that high HORMAD1...
Abstract Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism toward the consumption extracellular proteins, including matrix‐derived components as nutrient sources. The mechanism pericellular matrix degradation by starved has been largely overlooked. Here it is shown that breast pancreatic patient‐derived xenograft explants increases one order magnitude upon amino acid growth factor deprivation. In addition, found collagenolysis requires invadopodia...
Abstract Background PI3K signaling is frequently activated in breast cancer and targeted by inhibitors. However, resistance of tumor cells to inhibition, often mediated receptor tyrosine kinases, commonly observed reduces the potency Therefore, new treatment strategies overcome inhibitors are urgently needed boost their efficacy. The phosphatase SHP2, which plays a crucial role mediating signal transduction between kinases both MAPK pathways, potential target for combination treatment....
Abstract Background Endocrine therapies targeting estrogen signaling have significantly improved breast cancer (BC) patient survival, although 40% of ERα-positive BCs do not respond to those therapies. Aside from genomic signaling, triggers non-genomic pathways by forming a complex containing methylERα/Src/PI3K, hallmark aggressiveness and resistance tamoxifen. We aimed confirm the prognostic value this investigated whether its could improve tumor response in vivo. Methods The interaction...
Early detection of cancer is critical in medical sciences, as the sooner a diagnosed, higher are chances recovery. Tumour cells characterized by specific volatile organic compounds (VOCs) that can be used biomarkers. Through olfactory associative learning, animals trained to detect these VOCs. Insects such ants have refined sense smell, and easily rapidly with conditioning. Using urine from patient-derived xenograft mice stimulus, we demonstrate individual learn discriminate odour healthy...
Abstract Resistance to endocrine therapy and CDK4/6 inhibitors, the standard of care (SOC) in estrogen receptor-positive (ER+) breast cancer, greatly reduces patient survival. Therefore, elucidating mechanisms sensitivity resistance SOC identifying actionable targets are urgently needed. Here, we show that causes DNA damage toxic PARP1 trapping upon generation a functional BRCAness (i.e., BRCA1/2 deficiency) phenotype, leading increased histone parylation reduced H3K9 acetylation, resulting...