A5040177173- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- Medical Imaging Techniques and Applications
- Neuroendocrine Tumor Research Advances
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- bioluminescence and chemiluminescence research
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Plant Genetic and Mutation Studies
- Lung Cancer Research Studies
- Radiopharmaceutical Chemistry and Applications
- Peptidase Inhibition and Analysis
- Computational Drug Discovery Methods
- Microtubule and mitosis dynamics
- Advanced Proteomics Techniques and Applications
- Cancer Research and Treatments
- Advanced Biosensing Techniques and Applications
- Machine Learning in Bioinformatics
- DNA and Nucleic Acid Chemistry
- Steroid Chemistry and Biochemistry
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- Chemical Reactions and Isotopes
- Signaling Pathways in Disease
Baylor College of Medicine
2021-2024
Breast Center
2023
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...
Abstract Genomic analysis has recently identified multiple ESR1 gene translocations in estrogen receptor alpha–positive (ERα+) metastatic breast cancer (MBC) that encode chimeric proteins whereby the ligand binding domain (LBD) is replaced by C-terminal sequences from many different partners. Here we functionally screened 15 fusions and 10 promoted estradiol-independent cell growth, motility, invasion, epithelial-to-mesenchymal transition, resistance to fulvestrant. RNA sequencing a...
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
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>
<p>RP-6306 treatment did not restore the sensitivity of T47D Palbo-R cells to palbociclib</p>
<p>Additional BCM-7441 in vivo experiment data</p>