A5100753119- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Angiogenesis and VEGF in Cancer
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Diagnosis and Treatment
- Medical Imaging Techniques and Applications
- Cytokine Signaling Pathways and Interactions
- Melanoma and MAPK Pathways
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Genetic factors in colorectal cancer
- Cancer Mechanisms and Therapy
- Sarcoma Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- Cancer Research and Treatments
- Protein Tyrosine Phosphatases
- Gastric Cancer Management and Outcomes
- Phagocytosis and Immune Regulation
Cho Ray Hospital
2015-2025
University of Colorado Denver
2015-2024
University of Colorado Cancer Center
2013-2024
University of Colorado Anschutz Medical Campus
2012-2023
Institute of Biomedical Science
2023
University of Southern California
2023
Da Nang Hospital
2023
Rush University Medical Center
2023
American Association of Orthodontists
2023
Moffitt Cancer Center
2021
Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor. Unfortunately, not every patient responds and acquired drug resistance inevitably develops in those who do respond. This study aimed define molecular mechanisms of crizotinib patients ALK(+) non-small cell lung cancer (NSCLC).We analyzed tissue obtained from 14 NSCLC showing evidence radiologic progression while on intrinsic crizotinib.Eleven had...
Abstract Purpose: Oncogenic gene fusions involving the 3′ region of ROS1 kinase have been identified in various human cancers. In this study, we sought to characterize fusion genes non–small cell lung cancer (NSCLC) and establish proteins as drug targets. Experimental Design: An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for rearrangement by FISH. This assay also used screen patients with NSCLC. positive samples, identity partner determined through inverse PCR...
Oncogenic TRK fusions induce cancer cell proliferation and engage critical cancer-related downstream signaling pathways. These occur rarely, but in a diverse spectrum of tumor histologies. LOXO-101 is an orally administered inhibitor the kinase highly selective only for family receptors. Preclinical models using TRK-fusion-bearing human-derived lines demonstrate inhibition fusion oncoprotein cellular vitro, growth vivo. The 41-year-old woman with soft-tissue sarcoma metastatic to lung was...
Abstract Purpose: Despite initial benefit from tyrosine kinase inhibitors (TKIs), patients with advanced non–small cell lung cancer (NSCLC) harboring ALK (ALK+) and ROS1 (ROS1+) gene fusions ultimately progress. Here, we report on the potential resistance mechanisms in a series of ALK+ ROS1+ NSCLC progressing different types and/or lines ROS1/ALK–targeted therapy. Experimental Design: We used combination next-generation sequencing (NGS), multiplex mutation assay, direct DNA sequencing,...
Abstract Purpose: Patients with advanced non–small cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment ALK inhibitors (ALKi). Analysis of cell-free circulating tumor DNA (cfDNA) may provide a noninvasive way to identify and actionable resistance mechanisms without an invasive biopsy. Methods: The Guardant360 (G360; Guardant Health) deidentified database NSCLC cases was queried 88 consecutive patients 96 plasma-detected fusions....
The targeting of oncogenic 'driver' kinases with small molecule inhibitors has proven to be a highly effective therapeutic strategy in selected non-small cell lung cancer (NSCLC) patients. However, acquired resistance targeted therapies invariably arises and is major limitation patient care. ROS1 fusion proteins are recently described class driver, NSCLC patients that express these fusions generally respond well ROS1-targeted therapy. In this study, we sought determine mechanisms inhibition....
Abstract Activated anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinases, through gene fusions, have been found in lung adenocarcinomas are highly sensitive to selective inhibitors. This study aimed at identifying the presence of these rearrangements human colorectal adenocarcinoma specimens using a 4-target, 4-color break-apart FISH assay simultaneously determine genomic status ALK ROS1. Among clinical cancer analyzed, rearrangement-positive cases for both were observed. The fusion...
Oncogenic kinase fusions of ALK, ROS1, RET, and NTRK1 act as drivers in human lung other cancers. Residual tumor burden following treatment ALK or ROS1+ cancer patients with oncogene-targeted therapy ultimately enables the emergence drug-resistant clones, limiting long-term effectiveness these therapies. To determine signaling mechanisms underlying incomplete cell killing oncogene-addicted cells, we investigated role EGFR drug-naïve cells harboring oncogene fusions. We defined three distinct...
Oncogenic rearrangements in RET are present 1%-2% of lung adenocarcinoma patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency against the kinase domain. Here, we demonstrate that ponatinib exhibits potent antiproliferative activity fusion-positive LC-2/ad cells and inhibits phosphorylation fusion protein signaling through ERK1/2 AKT. Using distinct dose escalation strategies, two ponatinib-resistant cell lines, PR1 PR2, were derived. PR2 lines retained expression, but...
Abstract Chromosomal rearrangements involving receptor tyrosine kinases (RTK) are a clinically relevant oncogenic mechanism in human cancers. These chimeric oncoproteins often contain the C-terminal kinase domain of RTK joined cis to various N-terminal, nonkinase fusion partners. The functional role N-terminal partner is poorly understood. Here, we show that distinct partners drive differential subcellular localization, which imparts cell signaling and properties different, ROS1...
Abstract Purpose: Approved therapies for EGFR exon 20, ERBB2 mutations, and NRG1 fusions are currently lacking non–small cell lung cancer other cancers. Tarloxotinib is a prodrug that harnesses tumor hypoxia to generate high levels of potent, covalent pan-HER tyrosine kinase inhibitor, tarloxotinib-effector (tarloxotinib-E), within the microenvironment. This tumor-selective delivery mechanism was designed minimize dose-limiting toxicities characteristic systemic inhibition wild-type EGFR....
Non–small-cell lung cancer (NSCLC) is a disease in which tumor growth commonly driven by alterations along the receptor tyrosine kinase–RAS-RAF–mitogen-activated protein kinase pathway. Consequently, activated kinases this axis represent attractive therapeutic targets. Activation of can occur via multiple mechanisms at genetic level, including mutation, amplification, and rearrangement/fusion with other genes. The two best-characterized gene fusion classes NSCLC are those that involve ALK...
Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing partners. Retrospective investigations suggest that treatment benefit response to ALK tyrosine inhibitors (TKIs) differs dependent on the variant present patient tumor. Therefore, understanding oncogenic signaling networks driven by different is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein...
Abstract Lung cancers bearing oncogenic EML4-ALK fusions respond to targeted tyrosine kinase inhibitors (TKIs; e.g., alectinib), with variation in the degree of shrinkage and duration treatment (DOT). However, factors that control this response are not well understood. While contribution immune system mediating immunotherapy has been extensively investigated, less is known regarding immunity TKI therapeutic responses. We previously demonstrated a positive association TKI-induced interferon...
Introduction: The pathogenesis for poor kidney outcomes in lupus nephritis (LN) remains uncertain. There is limited evidence on the association between angiotensin-converting enzyme (ACE) I/D polymorphism and LN with failure. Objectives: To determine distribution of ACE alleles genotypes correlation participants. Subjects Methods: A cross sectional study was conducted at Cho Ray Hospital (12/2021-07/2023). participants were stratified into 3 groups based function replacement therapy (KRT)...
Oncogenic
Patients with metastatic NSCLC bearing a ROS1 gene fusion usually experience prolonged disease control ROS1-targeting tyrosine kinase inhibitors (TKI), but significant clinical heterogeneity exists in part due to the presence of co-occurring genomic alterations. Here, we report on patient concurrent and KRAS p.G12C mutation at diagnosis who experienced short duration entrectinib, TKI. At progression, continued entrectinib started sotorasib, small molecule inhibitor p.G12C. A patient-derived...