A5043946489- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Breast Cancer Treatment Studies
- TGF-β signaling in diseases
- Cancer-related Molecular Pathways
- Cancer Treatment and Pharmacology
- Cancer Cells and Metastasis
- Growth Hormone and Insulin-like Growth Factors
- Colorectal Cancer Treatments and Studies
- Metabolism, Diabetes, and Cancer
- Chronic Lymphocytic Leukemia Research
- Melanoma and MAPK Pathways
- Fibroblast Growth Factor Research
- Cell Adhesion Molecules Research
- Lung Cancer Research Studies
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Cancer Risks and Factors
- Pancreatic and Hepatic Oncology Research
- Radiopharmaceutical Chemistry and Applications
The University of Texas Southwestern Medical Center
2018-2025
Southwestern Medical Center
2018-2025
Harold C. Simmons Comprehensive Cancer Center
1998-2025
University Hospital Complex Of Vigo
2025
Complexo Hospitalario Universitario A Coruña
2025
University of Houston
2024
Vanderbilt University
2014-2023
Vanderbilt-Ingram Cancer Center
2011-2023
Vanderbilt University Medical Center
2014-2023
Breast Cancer Research Foundation
2011-2023
The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) negative human epidermal growth factor 2 (HER2).In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy safety selective CDK4/6 inhibitor ribociclib combined with letrozole first-line treatment 668 postmenopausal women HR-positive, HER2-negative recurrent metastatic who had...
Transforming growth factor-β1 (TGF-β) can be tumor suppressive, but it also enhance progression by stimulating the complex process of epithelial-to-mesenchymal transdifferentiaion (EMT). The signaling pathway(s) that regulate EMT in response to TGF-β are not well understood. We demonstrate acquisition a fibroblastoid morphology, increased N-cadherin expression, loss junctional E-cadherin localization, and cellular motility as markers for TGF-β–induced EMT. expression dominant-negative Smad3...
We have studied the role of phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling in transforming growth factor β (TGFβ)-mediated epithelial to mesenchymal transition (EMT). In NMuMG mammary cells, exogenous TGFβ1 induced phosphorylation Akt at Ser-473 and <i>in vitro</i> activity against GSK-3β within 30 min. These responses were temporally correlated with delocalization E-cadherin, ZO-1, integrin β<sub>1</sub> from cell junctions acquisition spindle morphology. LY294002, an inhibitor p110...
BackgroundThe phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer. Here, we report updated efficacy safety data, together exploratory biomarker analyses, from the study.Patients methodsA total of 668 postmenopausal women HR+,...
Abstract Purpose: We undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout natural history hormone-dependent breast cancer and delineate functional roles most commonly detected alterations. Experimental Design: studied a total 249 tumor specimens from 208 patients. The include 134 ER-positive (ER+/HER2−) and, as controls, 115 ER-negative (ER−) tumors. ER+ samples consist 58 primary cancers 76 metastatic samples. All tumors were sequenced...
After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies TNBC cells suggest that chemotherapy-resistant populations stem-like (CSCs) self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown increase properties in human cells. We analyzed RNA expression matched pairs primary biopsies before after chemotherapy. Biopsies chemotherapy displayed...
Although some cancers are initially sensitive to EGFR tyrosine kinase inhibitors (TKIs), resistance invariably develops. We investigated mechanisms of acquired the TKI gefitinib by generating gefitinib-resistant (GR) A431 squamous cancer cells. In GR cells, reduced phosphorylation EGFR, ErbB-3, and Erk but not Akt. These cells also showed hyperphosphorylation IGFI receptor (IGFIR) constitutive association IRS-1 with PI3K. Inhibition IGFIR signaling disrupted PI3K restored ability...
Many breast cancers exhibit a degree of dependence on estrogen for tumor growth. Although several therapies have been developed to treat individuals with estrogen-dependent cancers, some tumors show de novo or acquired resistance, rendering them particularly elusive current therapeutic strategies. Understanding the mechanisms by which these develop resistance would enable development new and effective therapeutics. In order determine escape from hormone in receptor-positive (ER-positive)...
TGF-betas are potent inhibitors of epithelial cell proliferation. However, in established carcinomas, autocrine/paracrine TGF-beta interactions can enhance tumor viability and progression. Thus, we studied the effect a soluble Fc:TGF-beta type II receptor fusion protein (Fc:TbetaRII) on transgenic transplantable models breast cancer metastases. Systemic administration Fc:TbetaRII did not alter primary mammary latency MMTV-Polyomavirus middle T antigen mice. increased apoptosis tumors, while...
Abstract Purpose: Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features lacking. Experimental Design: We analyzed TILs RD clinically and molecularly characterized TNBCs NAC explored therapeutic strategies targeting combinations MEK inhibitors PD-1/PD-L1–targeted immunotherapy mouse...
We have investigated mechanisms of acquired resistance to the HER2 antibody trastuzumab in BT-474 human breast cancer cells.BT-474 xenografts established athymic nude mice were eliminated by trastuzumab. Continuous cell lines (HR for Herceptin resistant) generated from tumors that recurred presence continuous therapy.The isolated cells behaved resistant culture as well when reinjected into mice. They retained gene amplification and binding exquisitely sensitive peripheral blood mononuclear...
In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than alone among postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative advanced breast cancer. Whether overall would also be was not known.Here we report the results protocol-specified final survival, key secondary end point. Patients were randomly assigned 1:1 ratio to receive either or placebo...