A5077641115- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer therapeutics and mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Diagnosis and Treatment
- Cancer Cells and Metastasis
- Cancer Treatment and Pharmacology
- Peptidase Inhibition and Analysis
- Gastric Cancer Management and Outcomes
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Advanced Breast Cancer Therapies
- Cancer Mechanisms and Therapy
- Medical Imaging Techniques and Applications
- Ferroptosis and cancer prognosis
- Hippo pathway signaling and YAP/TAZ
- Cancer-related gene regulation
AstraZeneca (United States)
2023-2025
The University of Texas MD Anderson Cancer Center
2016-2024
Medical University of South Carolina
2014-2016
Thoracic Surgery Foundation
2014
MUSC Hollings Cancer Center
2014
Abstract Purpose: Osimertinib was initially approved for T790M-positive non–small cell lung cancer (NSCLC) and, more recently, first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. Experimental Design: Using cohorts from The University Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Center databases, we collected clinical data patients treated with osimertinib. Molecular profiling analysis performed at the time...
Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver non-small cell lung cancer (NSCLC)1-3. Targeted therapies approved for patients with 'classical' a small number of other mutations4-6. However, effective have not been identified additional EGFR mutations. Furthermore, the frequency effects atypical on drug sensitivity unknown1,3,7-10. Here we characterize mutational landscape 16,715 EGFR-mutant NSCLC, establish structure-function...
Background Non-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome. Methods Three cohorts of NSCLC with (n=4189 total) were analyzed. Two advanced treated ICB monotherapy [MD Anderson (MDACC; n=172) Flatiron Health-Foundation...
Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which emerges through EGFR-independent mechanisms, such as pathways that promote epithelial-to-mesenchymal transition (EMT). Through an integrated transcriptomic, proteomic, and drug screening approach, we identified activation the yes-associated protein (YAP) forkhead box M1 (FOXM1) axis driver EMT-associated EGFR TKI...
We report a phase II study of 50 advanced non-small cell lung cancer (NSCLC) patients with point mutations or insertions in EGFR exon 20 treated poziotinib (NCT03066206). The achieved its primary endpoint, confirmed objective response rates (ORRs) 32% and 31% by investigator blinded independent review, respectively, median progression-free survival 5.5 months. Using preclinical studies, silico modeling, molecular dynamics simulations, we found that sensitivity was highly dependent on the...
PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with exon 20 mutant advanced NSCLC a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients were enrolled to receive at dose 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans performed least 28 days from initial...
8005 Background: Osimertinib (osi) is a third-generation, central nervous system-active EGFR-TKI, that potently and selectively inhibits EGFR-TKI sensitizing EGFR T790M resistance mutations. Adj osi (3 years [yrs]) recommended for resected EGFRm stage IB–IIIA NSCLC, based on significant improvements in disease-free survival (DFS) overall (OS) the Phase III ADAURA study (NCT02511106). A trend towards an increased DFS event rate beyond 3 yrs suggests some pts may benefit from longer adj...
Approximately 4% of NSCLC harbor BRAF mutations, and approximately 50% these are non-V600 mutations. Treatment tumors harboring mutations is challenging because functional heterogeneity lack knowledge regarding their clinical significance response to targeted agents.We conducted an integrative analysis using genomic profiles BRAF-mutant from the Guardant360 database. were categorized by clonality class (1 2: RAS-independent; 3: RAS-dependent). Cell viability assays performed in Ba/F3 models....
Abstract Background In FLAURA2, 1L osi with addition of platinum-pemetrexed chemotherapy (osi + CTx) significantly improved PFS vs alone in pts EGFRm advanced NSCLC. Prior FLAURA analyses showed detected BL plasma to be prognostic and early clearance correlated outcomes. We explored correlation detection, its clearance, FLAURA2 determine potential identify who derive particular benefit from CTx. Methods Treatment-naïve (Ex19del or L858R) NSCLC were randomized CTx 80 mg once daily [QD]...
Osimertinib—a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor—is recommended as adjuvant therapy for resected stage IB–IIIA receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of years treatment suggests that some patients may benefit from longer osimertinib treatment. We therefore...
9052 Background: Immune checkpoint blockade has led to unprecedented durable clinical benefit in metastatic non-small cell lung cancer (NSCLC), but response rates are low for patients with targetable driver mutations. EGFR and HER-2 exon 20 mutations account ~4% of NSCLC, outcomes these when treated immune have not been previously reported. Methods: We queried GEMINI, a MD Anderson Lung Cancer Moon Shot funded database prospective collection information 19, 20, 21 inhibitors. assessed...