A5057122527- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Breast Cancer Treatment Studies
- DNA Repair Mechanisms
- Estrogen and related hormone effects
- Effects of Radiation Exposure
- BRCA gene mutations in cancer
- Cancer Treatment and Pharmacology
- Lung Cancer Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Nuclear Structure and Function
- Ultrasound and Hyperthermia Applications
- Click Chemistry and Applications
- Bioactive Compounds and Antitumor Agents
- Radiation Therapy and Dosimetry
- Neuroendocrine Tumor Research Advances
- HER2/EGFR in Cancer Research
- Molecular Biology Techniques and Applications
- Enzyme Structure and Function
- Reproductive Physiology in Livestock
- Ferroptosis and cancer prognosis
National Institutes of Health
2024
Center for Cancer Research
2024
National Cancer Institute
2024
University of Michigan
2019-2022
New York University
2020
New England Disabled Sports
2007
Increased rates of locoregional recurrence are observed in patients with basal-like breast cancer (BC) despite the use radiation therapy (RT); therefore, approaches that result radiosensitization BC critically needed. Using patients' tumor gene expression data from 4 independent sets, we correlated to find genes significantly early after RT. The highest-ranked gene, TTK, was most highly expressed across multiple sets. Inhibition TTK by both genetic and pharmacologic methods enhanced...
Abstract Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), local rates 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there clear need intensification therapy, including radiation. Inhibition DNA repair protein PARP1 has had little efficacy as single agent outside studies restricted to BRCA mutations; however, inhibition (PARPi) may lead radiosensitization aggressive tumor types. Thus, this study...
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor-positive (ER+) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy multiple preclinical cancer models.Transcriptomic proteomic analyses were used identify significantly altered pathways after CDK4/6i. Clonogenic assays quantify enhancement ratio (rER). DNA damage was...
Standard radiation therapy (RT) does not reliably provide locoregional control for women with multinode-positive breast cancer and triple-negative (TNBC). We hypothesized that CDK4/6 inhibition (CDK4/6i) would increase the radiosensitivity only of estrogen receptor-positive (ER+) cells, but also TNBC expresses retinoblastoma (RB) protein. found CDK4/6i radiosensitized RB WT (n = 4, enhancement ratio [rER]: 1.49-2.22) failed to radiosensitize RB-null 3, rER: 0.84-1.00). expression predicted...
Canonical RAS signaling, including PI3K/AKT- and RAF/MEK-dependent activities, results mainly from RAS•GTP interaction with its effectors at the plasma membrane. Here, we identified a fundamental, oncogenic, noncanonical activity that increases XPO1-dependent export of nuclear protein cargo into cytoplasm is independent PI3K/AKT RAF/MEK signaling. This RAS-dependent step acts downstream XPO1 binding to mediated by perinuclear complex between RanGAP1 facilitates hydrolysis Ran•GTP Ran•GDP,...
Patients with radioresistant breast cancers, including a large percentage of women triple negative cancer (TNBC), demonstrate limited response to radiation (RT) and increased locoregional recurrence; thus, strategies increase the efficacy RT in TNBC are critically needed. We that pan Bcl-2 family inhibition (ABT-263, rER: 1.52-1.56) or Bcl-xL specific (WEHI-539, A-1331852; 1.31-2.00) radiosensitized wild-type
Abstract The majority of RAS oncogenic activity is thought to be mediated by its canonical signaling, mainly via RAS-GTP interactions with effectors RAF and PI3K at the plasma membrane, which respectively activate MEK/ERK AKT/mTOR pathways. However, in this study, we have identified a new, fundamental, pro-oncogenic, non-canonical that increases Exportin 1 (XPO1)-dependent export nuclear proteins into cytoplasm independent RAF/MEK PI3K/AKT signaling. protein machinery known depend on...
Abstract Purpose: Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC) local rates <70% at 5 years these patients. Given the unsatisfactory outcomes, there clear need for intensification therapy, including radiation, Inhibition poly(adenosine diphosphate-ribose) polymerase 1 (PARP1), DNA repair protein, represents novel and promising strategy radiosensitizing aggressive tumors. The purpose this study was to investigate...
Abstract Background: Basal-like breast cancer (BC) has the highest rates of local recurrence despite use radiation therapy. Therefore, approaches for radiosensitization are critically needed patients with this subtype BC. Methods: Four independent datasets were used to correlate gene expression (LR) and Kaplan-Meier analysis validated impact TTK on LR. The METABRIC dataset was determine in BC subtypes. Clonogenic survival assays cell lines after inhibition (TTKi). Mouse models assess TTKi...
<p>Captions for Supplementary Figures 1-9</p>
<p>Supplementary Materials and Methods Section</p>
<p>Supplementary Figures 1-9 and Supplementary Tables 1-6</p>
<p>Supplementary Figures 1-9 and Supplementary Tables 1-6</p>
<p>Captions for Supplementary Figures 1-9</p>
<p>Supplementary Materials and Methods Section</p>
<div>AbstractPurpose:<p>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor–positive (ER<sup>+</sup>) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy multiple preclinical cancer models.</p>Experimental Design:<p>Transcriptomic proteomic analyses were used identify significantly...
<div>AbstractPurpose:<p>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor–positive (ER<sup>+</sup>) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy multiple preclinical cancer models.</p>Experimental Design:<p>Transcriptomic proteomic analyses were used identify significantly...
<p>Enhancement ratios and toxicity for IBC clonogenic survival assays. Average radiation enhancement ratio (rER) values are shown each treatment in SUM-190 (A), MDA-IBC-3 (B), SUM-149 (C) cells.</p>
<p>Ki67 and p16 levels are decreased in tumors from animals treated with radiation combination PARP-inhibitor radiation. SUM-190 xenograft that were harvested mice at the completion of long-term vivo study. Protein expression assessed by immunohistochemical staining. Levels Ki67, a marker proliferation, significantly all treatment groups (A), RT-alone (B). Representative images each group shown (C,D). (* p < 0.05, ** <0.01, *** 0.001)</p>
<p>Extended methods for immunohistochemistry. Antibodies used in immunohistochemistry experiments are listed with each of the corresponding dilutions, retrieval techniques, and positive controls.</p>
<p>Higher doses of olaparib are sufficient to inhibit PAR formation in BRCA1-mutant SUM-149 cells. At higher concentrations (1μM), combination treatment PARP1 inhibition and radiation decreases a comparable manner lower (20nM) cells.</p>
<p>Higher doses of olaparib are sufficient to inhibit PAR formation in BRCA1-mutant SUM-149 cells. At higher concentrations (1μM), combination treatment PARP1 inhibition and radiation decreases a comparable manner lower (20nM) cells.</p>