A5066519998- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Advanced Breast Cancer Therapies
- T-cell and B-cell Immunology
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
Sidney Kimmel Cancer Center
2023-2024
Thomas Jefferson University
2023-2024
Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants, including relapsed tumors,...
Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate maintain hematopoiesis, increasing their susceptibility DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, prevent aging-driven dysregulation unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar fork reversal biochemical functions, Zranb3 Smarcal1, have surprisingly...
Clinical trials with single-agent venetoclax/ABT-199 (anti-apoptotic BCL2 inhibitor) revealed that diffuse large B-cell lymphoma (DLBCL) is not solely dependent on for survival. Gaining insight into pathways/proteins increase venetoclax sensitivity or unique vulnerabilities in venetoclax-resistant DLBCL would provide new potential treatment avenues. Therefore, we generated acquired cells and evaluated these together intrinsically -sensitive lines. We identified resistance mechanisms,...
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>