A5005870511- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Cancer-related Molecular Pathways
- Breast Cancer Treatment Studies
- Ocular Oncology and Treatments
- Metastasis and carcinoma case studies
- Polyomavirus and related diseases
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
Georgetown University
2019-2023
Georgetown University Medical Center
2020-2023
Georgetown-Howard Universities Center for Clinical and Translational Science
2022
University of Southern California
2014-2015
Background: CDK4/6 inhibitors (CDKi) have improved disease control in hormone-receptor-positive, HER2-negative metastatic breast cancer, but most patients develop progressive disease. Methods: We asked whether host stromal senescence after inhibition affects seeding and growth of CDKi-resistant mammary cancer cells by using the p16-INK-ATTAC mouse model inducible senolysis. Results: Palbociclib pretreatment naïve mice increased lung syngeneic cells, this effect was reversed depletion...
CDK4/6 inhibitors are used in the treatment of advanced estrogen receptor (ER)(+) breast cancer. Their efficacy ER(-) and early-stage cancer is currently under investigation. Here, we show that palbociclib, a inhibitor, can inhibit both progression ductal carcinoma situ (DCIS) growth invasive disease an basal model (MCFDCIS) ER(+) luminal (MCF7 intraductal injection). In MCFDCIS cells, palbociclib repressed cell-cycle gene expression, inhibited proliferation, induced senescence, normalized...
Patients with hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer have benefitted from treatment palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor capable of selectively targeting mechanisms cell cycle progression that contribute to tumor proliferation. Palbociclib use in this setting demonstrates improved progression-free survival when given combination aromatase inhibitors or fulvestrant.The authors describe the current state research surrounding...
Abstract BRCA1 associated protein-1 (BAP1) functions as a tumor suppressor gene by modulating fundamental cellular mechanisms such cell cycle progression and growth. Inactivating germline mutations of BAP1 predispose to multiple cancers including uveal cutaneous melanoma well malignant mesothelioma. In the present study we document family with novel mutation (g.1777C>T) that results in expression truncated protein. Family members this demonstrated primary clinical phenotype autosomal...
<p>Palbociclib's stromal impact and cancer outcomes</p>
<p>MUC16 and Tumor cell Death</p>
<p>Supplementary Methods: Supplementary Table 1 and 2</p>
<p>Palbociclib's transcriptomic effects on tumors</p>
<p>Palbociclib in the MIND Model</p>
<div>Abstract<p>CDK4/6 inhibitors are used in the treatment of advanced estrogen receptor (ER)(+) breast cancer. Their efficacy ER(−) and early-stage cancer is currently under investigation. Here, we show that palbociclib, a CDK4/6 inhibitor, can inhibit both progression ductal carcinoma <i>in situ</i> (DCIS) growth invasive disease an basal model (MCFDCIS) ER(+) luminal (MCF7 intraductal injection). In MCFDCIS cells, palbociclib repressed cell-cycle gene expression,...
<div>Abstract<p>CDK4/6 inhibitors are used in the treatment of advanced estrogen receptor (ER)(+) breast cancer. Their efficacy ER(−) and early-stage cancer is currently under investigation. Here, we show that palbociclib, a CDK4/6 inhibitor, can inhibit both progression ductal carcinoma <i>in situ</i> (DCIS) growth invasive disease an basal model (MCFDCIS) ER(+) luminal (MCF7 intraductal injection). In MCFDCIS cells, palbociclib repressed cell-cycle gene expression,...
<p>Supplementary Methods: Supplementary Table 1 and 2</p>
<p>Adverse events related to palbociclib treatment</p>
<p>Palbociclib's stromal impact and cancer outcomes</p>
<p>Canonical effects of CDK4/6 inhibition</p>
<p>Palbociclib treated 3D time course</p>
<p>MUC16 and Tumor cell Death</p>
<p>Palbociclib's transcriptomic effects on tumors</p>
<p>Palbociclib in the MIND Model</p>
<p>Palbociclib treated 3D time course</p>
<p>Canonical effects of CDK4/6 inhibition</p>
<p>Adverse events related to palbociclib treatment</p>
OBJECTIVES/GOALS: The objective of my study is to test overall hypothesis that CDK4/6 inhibitor-induced cellular senescence has long-lasting consequences on the tumor microenvironment affect growth and disease progression. METHODS/STUDY POPULATION: There a lack mechanistic understanding crosstalk drug effects different pathways. One less-studied consequence inhibitors (CDKI) their ability induce in non-malignant host cells (“stroma”), which causes secretion plethora proteins have lasting...