A5001373717- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Genetic factors in colorectal cancer
- Breast Cancer Treatment Studies
- Cancer Treatment and Pharmacology
- Gastric Cancer Management and Outcomes
- Peptidase Inhibition and Analysis
- Colorectal Cancer Treatments and Studies
- Lung Cancer Research Studies
- Advanced Biosensing Techniques and Applications
- Ubiquitin and proteasome pathways
- BRCA gene mutations in cancer
- Cancer Cells and Metastasis
- Chronic Lymphocytic Leukemia Research
- Glycosylation and Glycoproteins Research
- Sphingolipid Metabolism and Signaling
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- Genomics and Rare Diseases
- Advanced Proteomics Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Cell Adhesion Molecules Research
Washington University in St. Louis
2016-2025
Alvin J. Siteman Cancer Center
2015-2023
Saint Louis University
2022
Dana-Farber Cancer Institute
2018-2019
Baylor College of Medicine
2015-2019
Dana-Farber Brigham Cancer Center
2019
Brigham and Women's Hospital
2019
Magee-Womens Hospital
2019
McGill University Health Centre
2019
Institut Gustave Roussy
2019
To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five (RUNX1, CBFB, MYH9, MLL3 SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated luminal A status, low-grade histology...
Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 using vitro kinase assays, protein structure analysis, cell culture, and xenograft experiments. Seven are activating including G309A, D769H, D769Y, V777L, P780ins, V842I, R896C. in-frame deletion 755-759, which is homologous to EGF receptor (EGFR) exon 19 deletions, had a...
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained high fidelity. However, at single-nucleotide level, variable numbers PDX-specific somatic events documented, although they only rarely functionally significant. Variant allele frequencies often preserved in PDXs, demonstrating that clonal...
Purpose Detection of specific molecular alterations in tumors guides the selection effective targeted treatment patients with several types cancer. These may occur other tumor for which efficacy therapy remains unclear. The MyPathway study evaluates and safety selected therapies that harbor relevant genetic but are outside current labeling these treatments. Methods ( ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study. Patients...
Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal (IDBC). Despite clinical and pathologic differences, ILBC still treated as IDBC. We aimed to identify genomic alterations in with potential implications.From an initial 630 primary tumors, we interrogated oncogenic substitutions insertions deletions of 360 genes genome-wide copy number aberrations 413 170 samples, respectively, correlated those findings clinicopathologic outcome...
<h3>Importance</h3> Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. <h3>Objective</h3> To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. <h3>Design, Setting, Participants</h3> In randomized, controlled, open-label NEfERT-T trial conducted...
Abstract The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction the S310F, L755S, V777L, V842I, L866M into colon epithelial cells increased signaling pathways anchorage-independent cell growth, indicating that they are activating mutations. these cancer lines produced resistance to cetuximab panitumumab by sustaining MAPK phosphorylation. mutants potently inhibited low nanomolar doses irreversible...
Abstract Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) detection. Experimental Design: Tumor tissue positive for was required eligibility. Neratinib...
The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).Patients centrally confirmed HER2+ BC were randomly assigned 3:1 T-DM1 or TH received 3.6 mg/kg IV every 3 weeks for 17 cycles T 80 mg/m2 H once week × 12 (4 load →2 mg/kg), followed by...
Her2/neu (Her2) is a tyrosine kinase belonging to the EGF receptor (EGFR)/ErbB family and overexpressed in 20-30% of human breast cancers. We sought characterize Her2 signal transduction pathways further by using MS-based quantitative proteomics. Stably transfected cell lines overexpressing or empty vector were generated, effect an EGFR selective inhibitor, PD168393, on these cells was characterized. Quantitative measurements obtained 462 proteins SILAC (stable isotope labeling with amino...
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,...
•Pertuzumab + trastuzumab produced a response in 60% (9/15) of patients with HER2-amplified/overexpressing salivary cancer.•Stable disease was observed patient HER2-mutated cancer treated pertuzumab trastuzumab.•Vismodegib, vemurafenib, and atezolizumab responses tumors matched genomic alterations.•Safety for each treatment consistent previously reported safety profiles.•Results support use molecular profiling to identify effective chemotherapy-free targeted treatments cancers....
•CONTROL trial investigated antidiarrheal strategies including dose escalation in neratinib-treated patients with early HER2+ breast cancer.•Preemptive prophylaxis and reduced the rate, severity, duration of grade 3 diarrhea compared ExteNET.•Lower diarrhea-related discontinuations reductions multiple cohorts ExteNET suggested improved tolerability.•Neratinib is a particularly promising strategy as it eliminates mandatory related side-effects. BackgroundNeratinib an irreversible pan-HER...