Bryanna L. Norden
A5028144031- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Viral-associated cancers and disorders
- Fibroblast Growth Factor Research
- Advanced biosensing and bioanalysis techniques
- PI3K/AKT/mTOR signaling in cancer
- Studies on Chitinases and Chitosanases
- Animal Virus Infections Studies
- IgG4-Related and Inflammatory Diseases
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Metastasis and carcinoma case studies
- Chromosomal and Genetic Variations
- T-cell and Retrovirus Studies
- RNA modifications and cancer
- Extracellular vesicles in disease
- Melanoma and MAPK Pathways
- Metabolism, Diabetes, and Cancer
- Biochemical and Molecular Research
- Eosinophilic Disorders and Syndromes
- Galectins and Cancer Biology
- Circular RNAs in diseases
- interferon and immune responses
Massachusetts General Hospital
2023-2025
Harvard University
2023-2025
Abstract KRASG12C inhibitors, like sotorasib and adagrasib, potently selectively inhibit through a covalent interaction with the mutant cysteine, driving clinical efficacy in tumors. Because amino acid sequences of three main RAS isoforms—KRAS, NRAS, HRAS—are highly similar, we hypothesized that some inhibitors might also target NRASG12C and/or HRASG12C, which are less common but critical oncogenic driver mutations Although were selective for KRASG12C, others inhibited HRASG12C. Notably, was...
FGFR inhibitors are effective in FGFR2-altered cholangiocarcinoma, leading to approval of reversible inhibitors, pemigatinib and infigratinib, an irreversible inhibitor, futibatinib. However, acquired resistance develops, limiting clinical benefit. Some mechanisms have been reported, including secondary FGFR2 kinase domain mutations. Here, we sought establish the landscape inhibition validate findings model systems.
Abstract Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element overexpressed in carcinomas high-risk precursors during carcinogenesis with negligible expression normal tissues, suggesting ORF1p could...
PIK3CA mutations occur in ∼8% of cancers, including ∼40% HR-positive breast where the PI3K-alpha (PI3Kα)-selective inhibitor alpelisib is FDA approved combination with fulvestrant. Although prior studies have identified resistance mechanisms, such as PTEN loss, clinically acquired to PI3Kα inhibitors remains poorly understood. Through serial liquid biopsies and rapid autopsies 39 patients advanced cancer developing inhibitors, we observe that 50% acquire genomic alterations within PI3K...
Abstract Purpose: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as key suppressor of apoptotic response to MEKi. Patients and Methods: We conducted dose escalation study (NCT02079740) the inhibitor navitoclax MEKi trametinib patients with tumors expansion cohorts for: pancreatic, gynecologic (GYN), non–small cell lung cancer (NSCLC), other cancers harboring KRAS/NRAS mutations....
Abstract Purpose: Antibody-drug conjugates (ADCs) harboring topoisomerase I (TOP1) inhibitor payloads have improved survival for patients with metastatic breast cancer (MBC). However, knowledge of ADC resistance mechanisms and potential impact on sequential use ADCs is limited. Here, we report the incidence characterization TOP1 mutations arising in setting MBC. Methods: Patients MBC treated available post-treatment plasma-based genotyping were included. mutation incidence, mutant allele...
Abstract Mutations in TP53 are observed across all tumor types and the vast majority missense mutations occurring within its DNA binding domain (DBD), resulting decreased target gene expression due to loss of DNA-binding affinity. Among them, Y220C mutation is ninth most frequent, accounting for 1.8% p53 mutations. Structural characterization this substitution has revealed that it creates a small crevice protein, compromising thermal stability impairing function effectively interact with...
Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring response. While proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity these applications. Long INterspersed Element-1 (LINE-1, L1) open reading frame 1 protein (ORF1p) is a transposable element overexpressed in carcinomas high-risk precursors during carcinogenesis with negligible detectable expression corresponding normal tissues,...
FGFR2 and FGFR3 show oncogenic activation in many cancer types, often through chromosomal fusion or extracellular domain mutation. alterations are most prevalent intrahepatic cholangiocarcinoma (ICC) bladder cancers, respectively, multiple selective reversible covalent pan-FGFR tyrosine kinase inhibitors (TKI) have been approved these contexts. However, resistance, due to acquired secondary mutations the FGFR2/3 domain, limits efficacy. Resistance is typically polyclonal, involving a...
<div>AbstractPurpose:<p>FGFR inhibitors are effective in FGFR2-altered cholangiocarcinoma, leading to approval of reversible FGFR inhibitors, pemigatinib and infigratinib, an irreversible inhibitor, futibatinib. However, acquired resistance develops, limiting clinical benefit. Some mechanisms have been reported, including secondary FGFR2 kinase domain mutations. Here, we sought establish the landscape inhibition validate findings model systems.</p>Experimental...
<p>Alternative resistance pathways</p>
<p>Alternative resistance pathways</p>
<div>AbstractPurpose:<p>FGFR inhibitors are effective in FGFR2-altered cholangiocarcinoma, leading to approval of reversible FGFR inhibitors, pemigatinib and infigratinib, an irreversible inhibitor, futibatinib. However, acquired resistance develops, limiting clinical benefit. Some mechanisms have been reported, including secondary FGFR2 kinase domain mutations. Here, we sought establish the landscape inhibition validate findings model systems.</p>Experimental...
<p>Calibration curves for “3rd Generation” Simoa assays.</p>
<p>Additional second-generation ORF1p Simoa assay measurements in healthy and cancer patients.</p>
<p>Assay validation for second-generation ORF1p Simoa assays.</p>
<p>Kaplan-Meier Survival Analysis by ORF1p.</p>
<p>Assay validation for second-generation ORF1p Simoa assays.</p>
<p>Screening of multimeric nanobodies for ORF1p detection with Simoa.</p>
<p>Circulating ORF1p levels in patients with IPMN</p>