Jacob B. Pilcher
A5036879801- Advanced Breast Cancer Therapies
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- Neuroscience of respiration and sleep
- Neuroendocrine regulation and behavior
- Lung Cancer Research Studies
- Infant Health and Development
Baylor College of Medicine
2024
Baylor University
2022
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...
<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>
<p>Hallmark pathways enriched in ER+ PDX tumors</p>
<p>WEE1 mRNA levels in relationship to patient outcome and endocrine therapy response</p>
<p>Hallmark pathways enriched in NeoPalAna patients</p>
<p>Analysis of E2-regulated genes located on chromosome 16 near ERα ChIP peaks in MCF7 cells from The Signaling Pathways Project</p>
<p>PKMYT1 mRNA significantly correlates with Ki67 in Luminal A and B breast cancer samples from the METABRIC cohort</p>
<p>Potential mechanisms of palbociclib resistance in T47D and MCF7 EDR Palbo-R cell lines</p>
<p>Correlation of PKMYT1 protein levels with Hallmark scores in ER+ breast cancer PDXs</p>
<p>Synergy and viability analysis of AZD1775 gemcitabine combination in T47D parental Palbo-R cells</p>