A5061588019- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- Medical Imaging Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Peptidase Inhibition and Analysis
- Neuroendocrine Tumor Research Advances
- Biotin and Related Studies
- Cancer, Lipids, and Metabolism
- Adenosine and Purinergic Signaling
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- bioluminescence and chemiluminescence research
- Cancer-related Molecular Pathways
- Radiopharmaceutical Chemistry and Applications
- Cancer Cells and Metastasis
- Bioinformatics and Genomic Networks
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Ferroptosis and cancer prognosis
- Lung Cancer Research Studies
AstraZeneca (Brazil)
2024
Baylor College of Medicine
2022-2024
AstraZeneca (Japan)
2024
AstraZeneca (United States)
2023-2024
Breast Center
2023
Abstract Microscaled proteogenomics was deployed to probe the molecular basis for differential response neoadjuvant carboplatin and docetaxel combination chemotherapy triple-negative breast cancer (TNBC). Proteomic analyses of pretreatment patient biopsies uniquely revealed metabolic pathways, including oxidative phosphorylation, adipogenesis, fatty acid metabolism, that were associated with resistance. Both proteomics transcriptomics sensitivity marked by elevation DNA repair, E2F targets,...
Abstract Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs not directly druggable because the C-terminal estrogen/anti-estrogen–binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, mass spectrometry (MS)–based kinase inhibitor pulldown assay (KIPA) was deployed to identify kinases upregulated by diverse...
Abstract Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients 22 ER+ cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth...
NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking pathways by fulvestrant (F), selective ER degrader, together with binimetinib (B), MEK inhibitor, promotes regression NF1-depleted
Triple-negative breast cancer (TNBC) constitutes 10%-15% of all tumors. The current standard care is multiagent chemotherapy, which effective in only a subset patients. original objective this study was to deploy mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) identify kinases elevated non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound-embedded core needle biopsies were obtained from 43 patients with TNBC...
Abstract Background: Multi-omics analysis is widely used in cancer diagnosis, prognosis and prediction of treatment response. Here we introduce the use targeted proteomics coupled with NGS as tools to assess oncogenic alterations along quantitative protein expression patients mCRC. Our panel included proteins that are antibody drug conjugates (ADCs) targets (ERBB 1-4, TROP2, CEACAM5 etc.) well involved sensitivity ADC payload (SLFN11, efflux pump, TOP1 etc.). Methods: The HORIZON III trial...
Abstract NF1 is a key tumor suppressor that represses both RAS and estrogen receptor-α (ER) signaling in breast cancer. Blocking pathways by fulvestrant (F), selective ER degrader (SERD), together with binimetinib (B), MEK inhibitor, promotes regression NF1-depleted ER+ models. We aimed to establish approaches determine how protein levels impact B+F treatment response improve our ability identify sensitive tumors. examined panel of PDX models DNA mRNA sequencing found more than half these...
Sixteen patient-derived xenografts (PDXs) were analyzed using a mass spectrometry (MS)-based kinase inhibitor pull-down assay (KIPA), leading to the observation that death-associated protein 3 (DAPK3) is significantly and specifically overexpressed in triple-negative breast cancer (TNBC) models. Validation studies confirmed enrichment of DAPK3 protein, both TNBC cell lines tumors, independent mRNA levels. Genomic knockout
<p>The Supplementary Material contains a cover page, 8 Figures and their legends.</p>
<div>Abstract<p>Transcriptionally active ESR1 gene fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs not directly druggable because the C-terminal estrogen/anti-estrogen binding domain is replaced with translocated in-frame partner sequences that confer constitutive transactivation. To discover alternative treatments, mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify kinases upregulated...
<p>The Supplementary Material contains a cover page, 8 Figures and their legends.</p>
<div>Abstract<p>Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER<sup>+</sup>) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients 22 ER<sup>+</sup> cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, estradiol (E2)...
<p>A model of PKMYT1 gene transcription regulated by ERα and E2F factors</p>
<p>Immunoblotting of MCF7 EDR and Palbo-R cell lines to validate p53 protein knockdown</p>
<p>KIPA-SureQuant in T47D parental and palbociclib-resistant cells</p>
<p>Statistical analyses of data in Figures 6B, 6C, and S3.</p>
<p>WEE1 mRNA levels in relationship to anastrozole and palbociclib response</p>
<p>MCF7 EDR Palbo-R cell line displays cross-resistance to two other CDK4/6 inhibitors, in addition being palbociclib-resistant</p>
<p>The combination of RP-6306 and gemcitabine increases apoptosis activates DNA damage signaling in palbociclib-resistant T47D cells</p>
<p>Synergy and viability analysis of RP-6306 5-FU combination in T47D parental Palbo-R cells</p>
<p>Effect of RB1 knockdown on E2-induced gene expression</p>
<p>WEE1 mRNA and protein levels in ER+ breast cancer PDXs</p>
<p>This file contains 19 Supplementary Figures.</p>
<p>Effect of knocking down mutant p53 and re-expressing wild-type (WT) in T47D Palbo-R cells on synergy viability to the RP-6306 gemcitabine combination</p>
<p>Converted Free Plasma Level of RP-6306 in treated BCM-7441 PDX mice</p>