A5022816998- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Lung Cancer Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Colorectal Cancer Treatments and Studies
- Synthesis and biological activity
- Melanoma and MAPK Pathways
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA modifications and cancer
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Physiological and biochemical adaptations
- Cancer Cells and Metastasis
- Ovarian cancer diagnosis and treatment
- 3D Printing in Biomedical Research
- Glioma Diagnosis and Treatment
- Biomimetic flight and propulsion mechanisms
- Barrier Structure and Function Studies
- Angiogenesis and VEGF in Cancer
- Fish biology, ecology, and behavior
- Protein Kinase Regulation and GTPase Signaling
- Medicinal Plant Pharmacodynamics Research
Dana-Farber Cancer Institute
2018-2022
Harvard University
2018-2022
Brigham and Women's Hospital
2022
Wellesley College
2018
Columbia University Irving Medical Center
2017
Abstract Purpose: The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by gene fusion in 1%–2% of non–small cell lung cancers (NSCLC) and rarely other cancer types. Selpercatinib highly selective inhibitor has recently been approved the FDA thyroid with activating fusions mutations. Molecular mechanisms acquired resistance to selpercatinib are poorly understood. Patients Methods: We studied patients treated on first-in-human clinical trial (NCT03157129) who were found...
In-frame insertions in exon 20 of HER2 are the most common mutations patients with non-small cell lung cancer (NSCLC), a disease which approved EGFR/HER2 tyrosine kinase inhibitors (TKI) display poor efficiency and undesirable side effects due to their strong inhibition wild-type (WT) EGFR. Here, we report HER2-selective covalent TKI, JBJ-08-178-01, that targets multiple activating mutations, including as well amplification. JBJ-08-178-01 displayed selectivity toward mutants over WT EGFR...
Abstract Purpose: Activating missense mutations of KRAS are the most frequent oncogenic driver events in lung adenocarcinoma (LUAD). However, isoforms highly heterogeneous, and data on potential isoform-dependent therapeutic vulnerabilities still lacking. Experimental Design: We developed an isogenic cell-based platform to compare properties specific actionability KRAS-mutant isoforms. In parallel, we analyzed clinicopathologic genomic from 3,560 patients with non–small cell cancer (NSCLC)...
Abstract RAS gene mutations are the most frequent oncogenic event in lung cancer. They activate multiple RAS-centric signaling networks among them MAPK, PI3K, and RB pathways. Within MAPK pathway, ERK1/2 proteins exert a bottleneck function for transmitting mitogenic signals activating cytoplasmic nuclear targets. In view of disappointing antitumor activity toxicity continuously applied MEK inhibitors patients with KRAS-mutant cancer, research has recently focused on as therapeutic targets...
RAF protein kinases are effectors of the GTP-bound form small guanosine triphosphatase RAS and function by phosphorylating MEK. We showed here that expression ARAF activated in a kinase-independent manner. Binding to displaced GTPase-activating NF1 antagonized NF1-mediated inhibition RAS. This reduced ERK-dependent increased RAS-GTP. By this mechanism, regulated duration consequences RTK-induced activation supported output RTK-dependent tumor cells. In human lung cancers with EGFR mutation,...
Small-cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next-generation sequencing (NGS) and by characterizing a representative patient-derived model. performed targeted NGS, as well comprehensive pathological evaluation, 11 smokers with clinically diagnosed SCLC. established model from one such patient (DFCI168) harboring an NRASQ61K mutation characterized the sensitivity of MEK TORC1/2 inhibitors. Despite...
A subset of drug-resistant EGFR -mutant MET -amplified lung cancer switches oncogenic dependence to and is treatable with inhibitor monotherapy.
Abstract Introduction: Non-small cell lung cancers harboring sensitizing gain-of-function mutations in the epidermal growth factor receptor (EGFR) are treated with small molecule EGFR kinase inhibitors including erlotinib and osimertinib. Unfortunately, clinical efficacy of these is limited by progression to drug resistance. Genomic amplification hepatocyte (MET) a prevalent mechanism resistance inhibitors. mutant MET co-dependent on signaling through kinases, whereby either oncogene can...
<div>AbstractPurpose:<p>Activating missense mutations of <i>KRAS</i> are the most frequent oncogenic driver events in lung adenocarcinoma (LUAD). However, KRAS isoforms highly heterogeneous, and data on potential isoform-dependent therapeutic vulnerabilities still lacking.</p>Experimental Design:<p>We developed an isogenic cell-based platform to compare properties specific actionability KRAS-mutant isoforms. In parallel, we analyzed clinicopathologic...
Supplementary Data from Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of <i>KRAS</i> Mutations in Non–Small Cell Lung Cancer
<div>AbstractPurpose:<p>Activating missense mutations of <i>KRAS</i> are the most frequent oncogenic driver events in lung adenocarcinoma (LUAD). However, KRAS isoforms highly heterogeneous, and data on potential isoform-dependent therapeutic vulnerabilities still lacking.</p>Experimental Design:<p>We developed an isogenic cell-based platform to compare properties specific actionability KRAS-mutant isoforms. In parallel, we analyzed clinicopathologic...
Supplementary Data from Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of <i>KRAS</i> Mutations in Non–Small Cell Lung Cancer
Supplementary Data from Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of <i>KRAS</i> Mutations in Non–Small Cell Lung Cancer
Supplementary Data from Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of <i>KRAS</i> Mutations in Non–Small Cell Lung Cancer
Supplementary Data from Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of <i>KRAS</i> Mutations in Non–Small Cell Lung Cancer
Supplementary Data from Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of <i>KRAS</i> Mutations in Non–Small Cell Lung Cancer
<div>Abstract<p>In-frame insertions in exon 20 of HER2 are the most common <i>HER2</i> mutations patients with non–small cell lung cancer (NSCLC), a disease which approved EGFR/HER2 tyrosine kinase inhibitors (TKI) display poor efficiency and undesirable side effects due to their strong inhibition wild-type (WT) EGFR. Here, we report HER2-selective covalent TKI, JBJ-08–178–01, that targets multiple activating mutations, including as well amplification. JBJ-08–178–01...
Supplementary Data from A Novel HER2-Selective Kinase Inhibitor Is Effective in HER2 Mutant and Amplified Non–Small Cell Lung Cancer
<p>Supplementary Methods</p>
<p>Supplemental Figure 2</p>
<p>Supplemental Figure 1</p>
<p>Supplementary Methods</p>
<p>Supplemental Figure 1</p>