Carmen Behrens
A5009105122- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Molecular Biology Techniques and Applications
- Medical Imaging and Pathology Studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Microtubule and mitosis dynamics
- MicroRNA in disease regulation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Occupational and environmental lung diseases
The University of Texas MD Anderson Cancer Center
2016-2025
University of Illinois Urbana-Champaign
2016-2023
Nestlé (Germany)
2023
Anderson University - South Carolina
2021
Center for Translational Molecular Medicine
2018-2020
National Cancer Center
2020
Scripps MD Anderson Cancer Center
2013-2020
Thoracic Surgery Foundation
2008-2018
The University of Texas Southwestern Medical Center
2000-2016
Baylor College of Medicine
2016
The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis genomic, transcriptomic, and proteomic data from early-stage chemorefractory identified three robust subsets dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), CDKN2A/B inactivation coupled with low expression NKX2-1 (TTF1) transcription factor (KC). further revealed biologically...
Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining chest cavity. To expand our understanding MPM, we conducted comprehensive integrated genomic study, including most detailed analysis BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined novel subtype with TP53 SETDB1 mutations extensive loss heterozygosity. also report strong expression immune-checkpoint gene VISTA in epithelioid strikingly higher than...
Background: Most lung cancers are attributed to smoking. These have been associated with multiple genetic alterations and the presence of preneoplastic bronchial lesions. In view such associations, we evaluated status specific chromosomal loci in histologically normal abnormal biopsy specimens from current former smokers nonsmokers. Methods: Multiple were obtained 18 smokers, 24 21 Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers used examine eight...
To understand the role of nuclear factor erythroid-2-related 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in non-small cell lung cancer (NSCLC), we studied their expression a large series tumors with annotated clinicopathologic data, including response to platinum-based adjuvant chemotherapy.We determined immunohistochemical Nrf2 cytoplasmic Keap1 304 NSCLCs its association patients' characteristics, 89 from patients who received neoadjuvant (n = 26) or chemotherapy 63). We...
Abstract Aldehyde dehydrogenase (ALDH) is a candidate marker for lung cancer cells with stem cell-like properties. Immunohistochemical staining of large panel primary non–small cell (NSCLC) samples ALDH1A1, ALDH3A1, and CD133 revealed significant correlation between ALDH1A1 (but not ALDH3A1 or CD133) expression poor prognosis in patients including those stage I N0 disease. Flow cytometric analysis lines patient tumors that most NSCLCs contain subpopulation elevated ALDH activity, this...
Abstract Purpose: Promising results in the treatment of non–small cell lung cancer (NSCLC) have been seen with agents targeting immune checkpoints, such as programmed death 1 (PD-1) or ligand-1 (PD-L1). However, only a select group patients respond to these interventions. The identification biomarkers that predict clinical benefit checkpoint blockade is critical successful translation agents. Methods: We conducted an integrated analysis three independent large datasets, including Cancer...
Abstract Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated correlates decreased total CD8 + T cells exhausted cell subpopulations murine human tumors. Collagen-induced exhaustion occurs through the receptor LAIR1, which is upregulated following CD18 interaction collagen, induces SHP-1. Reduction tumor deposition LOXL2...
Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated with tumor grade and metastasis in lung cancer, likely due to its role as a transcription factor epithelial-to-mesenchymal transition (EMT). Here, we modeled malignant transformation human bronchial epithelial cells (HBECs) determined that EMT ZEB1 are early, critical events cancer pathogenesis. Specific oncogenic mutations TP53 KRAS were required for HBECs engage machinery response microenvironmental...
Aggressive neuroendocrine lung cancers, including small cell cancer (SCLC) and non-small (NSCLC), represent an understudied tumor subset that accounts for approximately 40,000 new cases per year in the United States. No targeted therapy exists these tumors. We determined achaete-scute homolog 1 (ASCL1), a transcription factor required proper development of pulmonary cells, is essential survival majority cancers (both SCLC NSCLC) with features. By combining whole-genome microarray expression...
Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non-small cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the benefits of ACT in NSCLC.An 18-hub-gene prognosis signature was developed through systems biology approach, its prognostic value evaluated six independent cohorts. The then integrated with genome-wide (RNAi) data genetic aberration derive 12-gene...
Abstract Epithelial-to-mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features EMT states, we undertook an integrative approach combining mRNA, miRNA, DNA methylation, proteomic profiles of 38 cell populations representative the genomic heterogeneity in lung adenocarcinoma. The resulting data were integrated functional consisting invasiveness, adhesion, motility. A subset lines that readily defined as epithelial or...
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation neoantigens, were shown to alter tumor immunogenicity T-cell responses. Here, we performed sequencing the receptor (TCR) in 45 regions from 11 adenocarcinomas and observed substantial differences density clonality majority clones restricted individual regions. TCR ITH positively correlated predicted neoantigen ITH, suggesting that...
Abstract Activating mutations of K-ras are the most common oncogenic alterations found in lung cancer. Unfortunately, attempts to target K-ras–mutant tumors have thus far failed, clearly indicating need for new approaches patients with this molecular profile. We previously shown NF-κB activation, release IL6, and activation its responsive transcription factor STAT3 tumors, which was further amplified by tumor-enhancing effect chronic obstructive pulmonary disease (COPD)-type airway...
RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets treatment myriad important human diseases including cancer. However, the effective systemic in vivo delivery small interfering (siRNA) to tumors remains formidable challenge. Using robust self-assembly strategy, we develop unique nanoparticle (NP) platform composed solid polymer/cationic lipid hybrid core lipid-poly(ethylene glycol) (lipid-PEG) shell siRNA delivery. The...
Abstract Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the in lungs patients with NSCLC. Here, we report repertoire analysis cohort 236 early-stage NSCLC patients. attributes are associated clinicopathologic features, mutational and immune landscape. A considerable proportion most prevalent also uninvolved tumor-adjacent appear specific shared background mutations or viral...
Significance The success rate of therapeutic trials that target tumor antigens is quite limited. We demonstrate for the first time to our knowledge lung cancer cells have undergone epithelial-to-mesenchymal transition lose immunoproteasome expression, resulting in markedly reduced antigen presentation. Reduced expression was associated with and can predict poor outcome non-small cell carcinoma (NSCLC) patients. Induction IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment overcome this...
Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses a unique set clinically annotated early-stage LUADs better understand pathogenesis this disease identify relevant molecular markers.We WES 108 paired stage I-III normal tissues using Illumina HiSeq 2000 platform. Ten markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 Granzyme B) were profiled by imaging-based...
Abstract Little is known of the geospatial architecture individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing 186,916 cells from five early-stage LUADs and 14 multiregion normal tissues defined spatial proximities tumors. We show that cellular lineages, states, transcriptomic features geospatially evolve across regions to LUADs. also exhibit pronounced intratumor heterogeneity within single sites transcriptional lineage-plasticity...
Abstract Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, role of FA LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate FASN, rate-limiting enzyme synthesis, while being dispensable EGFR-mutant or wild-type LC, required for viability cells. Integrating lipidomic, transcriptomic functional analyses,...
Abstract While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), independent contribution quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study 394 NSCLC patients, utilize pre-treatment computed tomography (CT) 18 F-fluorodeoxyglucose positron emission (FDG-PET) establish a habitat imaging framework for assessing regional heterogeneity within individual...
For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) CTLA4 inhibitors and PD-1 or PD-L1 (hereafter, PD-(L)1 inhibitors) is associated higher rates of anti-tumour activity immune-related toxicities, when compared treatment alone. However, there are currently no validated biomarkers to identify which will benefit from ICB1,2. Here we show that NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical ICB...