A5013726855- Lung Cancer Treatments and Mutations
- Gastric Cancer Management and Outcomes
- Colorectal Cancer Treatments and Studies
- Lung Cancer Diagnosis and Treatment
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- HER2/EGFR in Cancer Research
- Cancer therapeutics and mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Quinazolinone synthesis and applications
- Ferroptosis and cancer prognosis
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Microwave-Assisted Synthesis and Applications
- Fibroblast Growth Factor Research
- Mycobacterium research and diagnosis
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
- Kruppel-like factors research
- Immune Cell Function and Interaction
- Lymphoma Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
Nanospectra Biosciences (United States)
2024
State Street (United States)
2024
Yale University
2019-2023
Yale Cancer Center
2021-2022
Abstract Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, role of FA LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate FASN, rate-limiting enzyme synthesis, while being dispensable EGFR-mutant or wild-type LC, required for viability cells. Integrating lipidomic, transcriptomic functional analyses,...
Treatment with anti–PD-1 and anti-PD-L1 therapies has shown durable clinical benefit in non–small cell lung cancer (NSCLC). However, patients NSCLC epidermal growth factor receptor (EGFR) mutations do not respond as well to treatment without an EGFR mutation. We show that EGFR-mutated expressed higher levels of CD73 compared WT tumors expression was regulated by signaling. lines were significantly more resistant T killing through suppression proliferation function. In a xenograft mouse model...
Abstract Osimertinib, a mutant-specific third-generation EGFR tyrosine kinase inhibitor, is emerging as the preferred first-line therapy for EGFR-mutant lung cancer, yet resistance inevitably develops in patients. We modeled acquired to osimertinib transgenic mouse models of EGFRL858R-induced adenocarcinoma and found that it mediated largely through secondary mutations EGFR—either C797S or L718V/Q. Analysis circulating free DNA data from patients revealed L718Q/V almost always occur context...
Abstract Purpose: The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. clinical efficacy of patients non–small cell lung cancer harboring L747_A750>P and other ex19dels is not known. Experimental Design: AACR GENIE database was interrogated characterize frequency individual relative variants, a multicenter retrospective cohort used compare outcomes for...
EGFR exon 19 deletion (Ex19Del) mutations account for approximately 60% of lung cancer-associated and include a heterogeneous group mutations. Although they are associated with benefit from tyrosine kinase inhibitors (TKI), the relative inhibitor sensitivity individual Ex19Del is unknown.Experimental Design: We studied TKI structural features common consequences patient outcomes on treatment.We found that L747-A750>P mutation, which represents about 4% all mutations, displays unique...
583 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy that accounts for approximately 80-90% of all primary liver cancers and projected to become the third leading cause cancer-related mortality by 2030. Previous work demonstrated human Fibroblast Growth Factor 19 (FGF19) was overexpressed in 20-30% HCC, thereby exerting oncogenic effect via signaling through its cognate receptors FGFR4, FGFR3, co-receptor Klotho b (KLB). Multiple selective covalent FGFR4 inhibitors have...
Activating FGFR3 alterations have been identified in up to 15-20% of muscle-invasive bladder cancer and metastatic urothelial carcinoma (mUC), as high 80% nonmuscle invasive cancers. germline mutations also associated with a variety skeletal dysplasias. Achondroplasia, the most common form dwarfism humans, results from G380R mutation FGFR3. The pan-FGFR inhibitor erdafitinib was approved for treatment mUC but is limited due FGFR isoform off-target toxicities development on-target gatekeeper...
<div>Abstract<p>Purpose: The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared the common ex19del, E746_A750del in preclinical models. clinical efficacy of patients with non-small cell lung cancer (NSCLC) harboring L747_A750>P and other ex19dels is not known. Design: AACR GENIE database was interrogated characterize frequency individual relative variants, a multi-center retrospective cohort used compare outcomes...
<p>Supplementary Figure S3. Progression Free Survival for patients with tumors harboring select exon 19 deletions treated second or later line osimertinib (T790M+). The point estimate median progression free survival associated each mutation is listed to the right of figure legend.</p>
<p>Supplementary Figure S2. Progression Free Survival for patients with tumors harboring select exon 19 deletions treated first-line osimertinib. The point estimate median progression free survival associated each mutation is listed to the right of figure legend.</p>
<p>Supplementary Figure S1. Multi-institution cohort of patients with tumors harboring EGFR Exon 19 deletions. Primary analyses were performed on E746_A750del and L747_A750>P, while investigation into additional uncommon variants was descriptive only. Patient numbers do not reflect the true prevalence each variant since this is selectively enriched for exon deletions.</p>
<p>Supplementary Figure S3. Progression Free Survival for patients with tumors harboring select exon 19 deletions treated second or later line osimertinib (T790M+). The point estimate median progression free survival associated each mutation is listed to the right of figure legend.</p>
<p>Supplementary Figure S2. Progression Free Survival for patients with tumors harboring select exon 19 deletions treated first-line osimertinib. The point estimate median progression free survival associated each mutation is listed to the right of figure legend.</p>
<p>Supplementary Figure S1. Multi-institution cohort of patients with tumors harboring EGFR Exon 19 deletions. Primary analyses were performed on E746_A750del and L747_A750>P, while investigation into additional uncommon variants was descriptive only. Patient numbers do not reflect the true prevalence each variant since this is selectively enriched for exon deletions.</p>
<div>AbstractPurpose:<p>The uncommon <i>EGFR</i> exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. The clinical efficacy of patients non–small cell lung cancer harboring L747_A750>P and other ex19dels is not known.</p>Design:<p>The AACR GENIE database was interrogated characterize frequency individual relative variants, a multicenter...
Abstract Mutant KRAS (KM) is the most common oncogene in lung cancer (LC). KM regulates several metabolic networks, but their role tumorigenesis still not sufficiently characterized to be exploited therapy. To identify networks specifically deregulated KMLC, we lipidome of genetically engineered LC mice, cell lines, patient derived xenografts and primary human samples. We also determined that EGFR-mutant (EGFR-MUT) LC, enriched triacylglycerides (TAG) phosphatidylcholines (PC). found...
Osimertinib, a mutant‐specific third generation EGFR TKI, is emerging as the preferred first‐line therapy for mutant lung cancer. Despite initial responses in patients, however, resistance inevitably develops over time. In order to investigate mechanisms of osimertinib, we modeled acquired this drug transgenic mouse models L858R ‐induced adenocarcinoma and found that it mediated largely through secondary mutations – either C797S or L718V/Q (Figure 1A 1B). Analysis circulating free DNA data...
<p>Cell-free DNA Mutation Dataset</p>
<p>Supplementary Methods, Supplementary Tables S1-5, and Figures S1-9</p>
<p>Cell-free DNA Mutation Dataset</p>