Francois Gonzalvez
A5104505047- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Chronic Lymphocytic Leukemia Research
- interferon and immune responses
- Cancer Immunotherapy and Biomarkers
- Protein Tyrosine Phosphatases
- Colorectal Cancer Treatments and Studies
- Cancer therapeutics and mechanisms
- Pharmacogenetics and Drug Metabolism
- Hepatitis C virus research
- Chronic Myeloid Leukemia Treatments
- Liver Disease Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- Immunotherapy and Immune Responses
- Lung Cancer Research Studies
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
Ariadne Diagnostics (United States)
2014-2023
Takeda (United States)
2021-2022
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non-small cell lung cancer (NSCLC) are insensitive to approved tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible TKI, was specifically designed potently inhibit oncogenic variants containing activating EGFRex20ins with selectivity over wild-type EGFR. The vitro and vivo activity evaluated engineered patient-derived models...
Abstract No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) insertion mutations. However, the function of mobocertinib on cancer still unclear. Here we conducted systematic characterization preclinical models understand activity profile against insertions. In cell lines, IC50 was...
Abstract In non-small cell lung cancer (NSCLC), multiple classes of activating mutations have been identified in EGFR and HER2 that vary widely their sensitivity to available tyrosine kinase inhibitors (TKIs). Erlotinib, gefitinib, afatinib are approved for use patients with the most common forms (ie, exon 19 deletions or L858R substitutions). However, no TKIs activated by any other mutation, including 20 insertions uncommon substitutions, class mutation (including insertions). As inhibition...
In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in epidermal growth factor receptor (EGFR) gene have few effective therapies because this subset mutants is generally resistant to most currently approved EGFR inhibitors. This report describes structure-guided design a novel series potent, irreversible inhibitors mutations, including V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led...
Abstract Introduction: The STING (STimulator of INterferon Genes) protein has been identified as an attractive target for cancer immunotherapy due to its central role in inducing T-cell mediated tumor control. Here we describe the preclinical characteristics novel agonist, ALG-031048, that demonstrates potent anti-tumoral activity vivo mouse models. Methods: Binding was determined using differential scanning fluorimetry (DSF). Cellular activation and cytokine release were assessed HEK 293T...
Stimulator of interferon genes (STING) agonists have shown potent anti-tumor efficacy in various mouse tumor models and the potential to overcome resistance immune checkpoint inhibitors (ICI) by linking innate acquired systems. First-generation STING are administered intratumorally; however, a systemic delivery route would greatly expand clinical use agonists. Biochemical cell-based experiments, as well syngeneic models, were used demonstrate anti-tumoral activity ALG-031048, novel agonist....
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<p>GSEA analysis of mobocertinib and T-DM1 treated tumors versus mobocertinib-only Genes involved in "INTERFERON ALPHA RESPONSE", "INFLAMMATORY GAMMA "IL2 STAT5 SIGNALING", "TNFA SIGNALING VIA NFKB" "IL6 JAK STAT3 SIGNALING" pathways HALLMARK gene sets.</p>
<p>Figure S4</p>
<p>GSEA analysis of mobocertinib and T-DM1 treated tumors versus mobocertinib-only Genes involved in "INTERFERON ALPHA RESPONSE", "INFLAMMATORY GAMMA "IL2 STAT5 SIGNALING", "TNFA SIGNALING VIA NFKB" "IL6 JAK STAT3 SIGNALING" pathways HALLMARK gene sets.</p>
<p>Figure S1</p>
<p>Figure S4</p>
<div>Abstract<p>No targeted treatments are currently approved for <i>HER2</i> exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (<i>HER2/ERBB2</i>) insertion mutations. However, the function of mobocertinib on cancer still unclear. Here we conducted systematic characterization preclinical models understand...
<p>GSEA analysis of mobocertinib acquired resistant tumors versus response Genes involved in "G2M CHECKPOINT", "MITOTIC SPINDLE" and "MTORC1 SIGNALING" pathways HALLMARK gene sets.</p>
<p>GSEA analysis of mobocertinib acquired resistant tumors versus response Genes involved in "G2M CHECKPOINT", "MITOTIC SPINDLE" and "MTORC1 SIGNALING" pathways HALLMARK gene sets.</p>
<div>Abstract<p>No targeted treatments are currently approved for <i>HER2</i> exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (<i>HER2/ERBB2</i>) insertion mutations. However, the function of mobocertinib on cancer still unclear. Here we conducted systematic characterization preclinical models understand...
<div>Abstract<p>Most <i>EGFR</i> exon 20 insertion (<i>EGFR</i>ex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting <i>EGFR</i>-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible TKI, was specifically designed potently inhibit oncogenic variants containing activating <i>EGFR</i>ex20ins...
<div>Abstract<p>Most <i>EGFR</i> exon 20 insertion (<i>EGFR</i>ex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting <i>EGFR</i>-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible TKI, was specifically designed potently inhibit oncogenic variants containing activating <i>EGFR</i>ex20ins...
<p>Supplementary Tables (S1-6) and Figures (S1-6)</p>