Meenakshi Anurag
A5024724100- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Advanced Proteomics Techniques and Applications
- Lung Cancer Treatments and Mutations
- Estrogen and related hormone effects
- Medical Imaging Techniques and Applications
- Neuroendocrine Tumor Research Advances
- Peptidase Inhibition and Analysis
- Cancer, Lipids, and Metabolism
- Biotin and Related Studies
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Adenosine and Purinergic Signaling
- Biochemical and Molecular Research
- Genetic factors in colorectal cancer
- Breast Cancer Treatment Studies
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Bioinformatics and Genomic Networks
Baylor College of Medicine
2016-2024
Dan L Duncan Comprehensive Cancer Center
2022-2023
Breast Center
2023
Sanford Burnham Prebys Medical Discovery Institute
2018
Washington University in St. Louis
2017-2018
University of Maryland, Baltimore
2017-2018
Mayo Clinic in Florida
2017-2018
WinnMed
2017-2018
Universidade Estadual de Campinas (UNICAMP)
2018
Kitasato University
2018
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued preserve post-translational modifications, including protein phosphorylation acetylation. Proteogenomics challenged standard cancer diagnoses, provided detailed analysis the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint...
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences perturbations to the p53 Wnt/β-catenin pathways, identified potential role for circRNAs in epithelial-mesenchymal transition, provided information about proteomic markers clinical genomic tumor subgroups, including relationships known druggable pathways. An extensive genome-wide...
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins phosphosites, prioritizes copy number drivers, highlights an oncogenic role for RNA processing genes. investigation mutual exclusivity between FAT1 truncating mutations 11q13.3 amplifications reveals dysregulated actin dynamics as common functional consequence. Phosphoproteomics characterizes two...
Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology both normal cancer cells. Advances mass spectrometry enable high-throughput, accurate, sensitive measurement of PTM levels to better understand their role, prevalence, crosstalk. Here, we analyze the largest collection proteogenomics data from 1,110 patients with profiles across 11 types (10 National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals...
Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying significant cis-effects and distal trans-effects quantified at RNA, protein, phosphoprotein levels. Salient observations include association point mutations copy-number alterations with rewiring protein interaction networks,...
Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%–20% cases have demonstrated durable responses from immune checkpoint blockade. To enhance efficacy immunotherapies, combination therapies suppressing multiple evasion mechanisms are increasingly contemplated. better understand cell surveillance and diverse tumor tissues, we comprehensively characterized landscape more 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic...
Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation prognosis. Independent validation prognostic was achieved data the METABRIC study. Previously established associations MAP3K1 PIK3CA mutations with luminal A status/favorable prognosis TP53 Luminal B/non-luminal tumors/poor were observed,...
Abstract Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics protein profiling including modifications mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a approach for core biopsies using tissue-sparing specimen processing microscaled proteomics. As demonstration, analyze needle from ERBB2 positive breast cancers before...
RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in receptor-positive (ER+) breast cancer, but their role disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified advanced endocrine treatment-resistant disease, encoded stable functional proteins. In examples, ESR1-e6>YAP1 ESR1-e6>PCDH11X, exons 1–6 were fused frame to C-terminal sequences from the partner gene. Functional properties include...
We report that neurofibromin, a tumor suppressor and Ras-GAP (GTPase-activating protein), is also an estrogen receptor-α (ER) transcriptional co-repressor through leucine/isoleucine-rich motifs are functionally independent of GAP activity. activity, in turn, does not affect ER binding. Consequently, neurofibromin depletion causes estradiol hypersensitivity tamoxifen agonism, explaining the poor prognosis associated with loss endocrine therapy-treated ER+ breast cancer....
Abstract Microscaled proteogenomics was deployed to probe the molecular basis for differential response neoadjuvant carboplatin and docetaxel combination chemotherapy triple-negative breast cancer (TNBC). Proteomic analyses of pretreatment patient biopsies uniquely revealed metabolic pathways, including oxidative phosphorylation, adipogenesis, fatty acid metabolism, that were associated with resistance. Both proteomics transcriptomics sensitivity marked by elevation DNA repair, E2F targets,...
DNA methylation plays a critical role in establishing and maintaining cellular identity. However, it is frequently dysregulated during tumor development closely intertwined with other genetic alterations. Here, we leveraged multi-omic profiling of 687 tumors matched non-involved adjacent tissues from the kidney, brain, pancreas, lung, head neck, endometrium to identify aberrant associated RNA protein abundance changes build Pan-Cancer catalog. We uncovered lineage-specific epigenetic drivers...
We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing presentation machinery activity, may inform patient selection for immunotherapy. Association analysis between MYC activity metformin treatment in both patients cell lines suggests potential role non-diabetic with elevated activity. PIK3R1 in-frame indels are associated AKT...
Non-clear cell renal carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis aggressive disease, therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, metabolic aberrations in RCC subtypes. RCCs high genome instability display overexpression IGF2BP3 PYCR1. Integration...
Purpose: This study was undertaken to conduct a comprehensive investigation of the role DNA damage repair (DDR) defects in poor outcome ER+ disease.Experimental Design: Expression and mutational status DDR genes breast tumors were correlated with proliferative response neoadjuvant aromatase inhibitor therapy trials (discovery dataset), outcomes METABRIC, TCGA, Loi datasets (validation datasets), patient-derived xenografts. A causal relationship between candidate endocrine treatment response,...
Abstract Significant endocrine therapy–resistant tumor proliferation is present in ≥20% of estrogen receptor–positive (ER+) primary breast cancers and associated with disease recurrence death. Here, we uncover a link between intrinsic therapy resistance dysregulation the MutL mismatch repair (MMR) complex (MLH1/3, PMS1/2), demonstrate direct role for loss to all classes therapy. We find that deficiency ER+ cancer abrogates CHK2-mediated inhibition CDK4, prerequisite responsiveness....
Unlike estrogen receptor (ER)-negative breast cancer, ER-positive cancer outcome is less influenced by lymphocyte content, indicating the presence of immune tolerance mechanisms that may be specific to this disease subset.A supervised analysis microarray data from ACOSOG Z1031 (Alliance) neoadjuvant aromatase inhibitor (AI) trial identified upregulated genes in Luminal (Lum) B cancers correlated with AI-resistant tumor proliferation (percentage Ki67-positive nuclei, Pearson r > 0.4) (33...
Abstract Protein kinases are frequently dysregulated and/or mutated in cancer and represent essential targets for therapy. Accurate quantification is essential. For breast treatment, the identification of protein kinase ERBB2 critical therapeutic decisions. While immunohistochemistry (IHC) current clinical diagnostic approach, it only semiquantitative. Mass spectrometry-based proteomics offers quantitative assays that, unlike IHC, can be used to accurately evaluate hundreds simultaneously....
Abstract Purpose Alterations to mismatch repair (MMR) pathways are a known cause of cancer, particularly colorectal and endometrial carcinomas. Recently, checkpoint inhibitors have been approved for use in MMR-deficient cancers any type (Prasad et al. JAMA Oncol 4:157–158, 2018). Functional studies breast cancer shown associations between MMR loss, resistance aromatase sensitivity palbociclib (Haricharan Cancer Discov 7:1168–1183, 2017). Herein, we investigate the clinical meaning deficiency...
We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated critical clinical outcomes in cancer. utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs. normal (AUROC = 0.995) tissue-of-origin 0.979). further investigate power on tasks not normally performed...
Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested early-stage disease.
Urothelial carcinoma in situ (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared high-grade papillary tumors are underexplored. RNA sequencing CIS, tumors, and normal urothelium showed lower immune marker expression tumors. We identified a 46-gene signature samples including selectively upregulated known druggable targets MTOR, TYK2, AXIN1, CPT1B, GAK, PIEZO1 downregulated BRD2 NDUFB2. High selected genes was significantly...