A5041255464- Colorectal Cancer Treatments and Studies
- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- Chromatin Remodeling and Cancer
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Gastric Cancer Management and Outcomes
- Lung Cancer Treatments and Mutations
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Histone Deacetylase Inhibitors Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Multiple Myeloma Research and Treatments
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Protein Kinase Regulation and GTPase Signaling
- Virus-based gene therapy research
- Microtubule and mitosis dynamics
- Ferroptosis and cancer prognosis
- Computational Drug Discovery Methods
- Cancer Cells and Metastasis
- HER2/EGFR in Cancer Research
- Pancreatic and Hepatic Oncology Research
- Genomics and Chromatin Dynamics
The University of Texas MD Anderson Cancer Center
2019-2025
The University of Texas Health Science Center at Houston
2021
How the
PURPOSE Acquired resistance to anti–epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on basis single-agent EGFRi trials and little is known about mechanisms combined with effective cytotoxic chemotherapy untreated patients. METHODS We analyzed paired plasma samples from patients RAS/BRAF/EGFR wild-type...
Enhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, comprehensive knowledge chromatin state patterns in tumour progression, heterogeneity these and imparted therapeutic opportunities remain poorly described.We performed epigenomic characterisation by mapping 222 profiles from 69 samples (33 adenocarcinomas, 4 adenomas, 21 matched normal tissues 11 colon cancer cell lines) for six histone modification marks: H3K4me3 Pol II-bound...
Abstract Purpose: AT-rich interactive domain 1A (ARID1A) is commonly mutated in colorectal cancer, frequently resulting truncation and loss of protein expression. ARID1A recruits MSH2 for mismatch repair during DNA replication. deficiency promotes hypermutability immune activation preclinical models, but its role patients with cancer being explored. Experimental Design: The sequencing gene expression profiling were extracted from Cancer Genome Atlas MD Anderson Center databases, validation...
Abstract MAPK pathway inhibitors (MAPKi) are increasingly used in the treatment of advanced colorectal cancer, but often produce short-lived responses patients. Although acquired resistance by de novo mutations tumors have been found to reduce response some patients, additional mechanisms underlying limited durability targeting therapy remain unknown. Here, we denote new contributory tumor biology and provide insight on impact plasticity response. Analysis MAPKi treated patients revealed...
Abstract Purpose: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated patients with mCRC. Experimental Design: We performed series vivo studies using mCRC tumor xenografts. Mice were randomized receive 5-fluoruracil (5-FU), irinotecan, or oxaliplatin (FOLFIRI FOLFOX), combination. Patients...
Abstract Purpose: BRAFV600E-mutated colorectal cancer (CRC) exhibits a strong correlation with DNA hypermethylation suggesting this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits methyltransferase activity, is not efficacious in BRAFV600E CRC vivo. Experimental Design: We randomized and treated mice implanted patient-derived tumor xenografts harboring mutation control, vemurafenib (BRAF inhibitor), or the combination. Comprehensive...
Abstract Background: BRAFV600E in colorectal cancer (CRC) defines a unique subgroup of patients with poor prognosis and scarcely benefit from BRAF inhibitor-based treatment. Interestingly, tumors demonstrated profound CpG island methylator phenotype (CIMP), suggesting extensive epigenetic dysregulation. Thus, we investigated epigenomic regulations this subset treatment-induced DNA demethylation. Methods: We treated six cell lines two patient-derived xenograft (PDX) models CRC vehicle,...
<div>Abstract<p>Purpose: Encorafenib plus cetuximab is an effective therapeutic option in chemorefractory <i>BRAFV600E </i>mCRC. However, there a need to improve the efficacy of this molecular targeted therapy and evaluate regimens suitable for untreated </i>mCRC patients. Experimental Design: We performed series <i>in vivo </i>studies using <i>BRAFV600E<sup></sup></i>mCRC tumor xenografts. Mice were randomized receive:...
<p>Differentially enriched hallmark gene sets after cytotoxic chemotherapy and targeted therapy of B1003b PDX tumor samples.</p>
<p>Differentially enriched hallmark gene sets after cytotoxic chemotherapy and targeted therapy of B1003b PDX tumor samples.</p>
<p>Graphical representation of adaptive epigenome reprogramming upon 5-azacitidine treatment in BRAFV600E CRC</p>
<div>AbstractPurpose:<p>BRAF<sup>V600E</sup>-mutated colorectal cancer exhibits a strong correlation with DNA hypermethylation, suggesting that this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits methyltransferase activity, is not efficacious in BRAF<sup>V600E</sup> <i>in vivo</i>.</p>Experimental Design:<p>We randomized and treated mice implanted patient-derived tumor xenografts...
<p>Differential methylation and histone marks upon 5-azacitidine treatment around 5mC-regulated genes</p>
<p>Chromatin state profiles of control and 5-azacitidine-treated samples</p>
<p>Proteomic analysis of histone post-translational modifications (PTMs), particularly lysine acetylation, upon 5-azacitidine treatment</p>
<p>Limited impact of 5-azacitidine treatment in gene expression changes</p>
<p>Combining anti-EGFR antibodies did not improve response to vemurafenib plus 5-azacitidine treatment.</p>
<p>Extended investigation of the combination 5-azacitidine and PRC inhibitors</p>
Abstract Colorectal cancer (CRC) is commonly treated with MAPK pathway inhibitors (MAPKi) including EGFRi, BRAFi, and most recently KRAS G12C inhibitors. However, clinical trials repeatedly demonstrate that durability of benefit short-lived in many patients. While genomic mechanisms acquired resistance have been described, this explains a small minority patients further research needed to determine the underlying biology limiting MAPKi therapy CRC. Potential responsible were explored using...
ABSTRACT The extent and function of chromatin state aberrations during colorectal cancer (CRC) progression is not completely understood. Here, by comprehensive epigenomic characterization 56 tumors, adenomas, their matched normal tissues, we define the dynamics states cancer. H3K27ac-marked active enhancer could distinguish between different stages CRC progression. By editing, present evidence that gains tumor-specific enhancers for crucial oncogenes, such as ASCL2 FZD10 , was excessive...
<p>Supplementary Table S1</p>