A5077706642- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Neuroendocrine Tumor Research Advances
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Chemical Reactions and Isotopes
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- BRCA gene mutations in cancer
- Occupational and environmental lung diseases
- Advanced biosensing and bioanalysis techniques
- Fibroblast Growth Factor Research
- Chromatin Remodeling and Cancer
- COVID-19 Clinical Research Studies
- COVID-19 Impact on Reproduction
- COVID-19 and healthcare impacts
- Cancer Diagnosis and Treatment
- Immune cells in cancer
Memorial Sloan Kettering Cancer Center
2017-2024
Cornell University
2017-2024
Southwest Medical University
2024
Washington University in St. Louis
2017
National Institutes of Health
2013
National Cancer Institute
2013
Center for Cancer Research
2013
New York University
2012
Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes defined by differential expression of ASCL1, NEUROD1, and POU2F3 (SCLC-A, -N, -P, respectively). To define the heterogeneity tumors their associated microenvironments across subtypes, we sequenced 155,098 transcriptomes from 21 human biospecimens, including 54,523 SCLC transcriptomes. We observe greater tumor diversity in than adenocarcinoma, driven canonical, intermediate, admixed subtypes. discover a...
PURPOSE Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb–mediated tumor lysis. Herein, we report phase I results of tarlatamab patients PATIENTS AND METHODS This study evaluated relapsed/refractory The primary end point was safety. Secondary points included antitumor activity by modified RECIST...
Abstract Purpose: Determine the 1-year progression-free survival (PFS) rate among patients with malignant pleural mesothelioma (MPM) receiving WT1 peptide vaccine galinpepimut-S after multimodality therapy versus those control adjuvants. Experimental Design: This double-blind, controlled, two center phase II trial randomized MPM surgery and another treatment modality to GM-CSF Montanide or alone. An improvement in PFS from 50% 70% was predefined efficacy threshold, 78 total were planned. The...
8510 Background: DLL3, an inhibitory Notch ligand, is a promising target as it highly expressed in SCLC compared to normal tissue. AMG 757, half-life extended BiTE immuno-oncology therapy, binds DLL3 on tumor cells and CD3 T cells, leading cell-dependent killing of tumors. Results from the first nine dosing cohorts showing preliminary efficacy 757 (confirmed partial response [PR], 14% pts) were previously presented. Here, updated safety, efficacy, pharmacokinetic data 10 ongoing phase 1...
Access to clinically relevant small cell lung cancer (SCLC) tissue is limited because surgical resection rare in metastatic SCLC. Patient-derived xenografts (PDX) and circulating tumor cell-derived (CDX) have emerged as valuable tools characterize Here, we present a resource of 46 extensively annotated PDX/CDX models derived from 33 patients with We perform multi-omic analyses, using targeted next-generation sequencing, RNA-sequencing, immunohistochemistry deconvolute the mutational...
Abstract Purpose: Recurrent small-cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted. Patients and Methods: This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients recurrent SCLC. Phase I primary objectives were to assess safety, tolerability, recommended II dose (RP2D). objective was overall response rate (ORR), secondary determining duration (DoR),...
PURPOSE Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine sensitivity. MATERIALS AND METHODS Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and subsequent cycles with paired both before again infusions. Tumor-informed analysis was carried out using CAncer Personalized Profiling deep Sequencing...
9060 Background: HER2 mutations are present in 3% of lung cancers. Response to immune checkpoint blockade (ICB) this subset cancers is unknown. We evaluate the landscape PD-L1 and tumor mutation burden (TMB) HER2-mutant (HER2m) their response ICB. Methods: Patients (pts) with advanced HER2m were identified retrospectively. expression was determined by immunohistochemistry (IHC); TMB estimated next-generation sequencing (NGS) using MSK-IMPACT. Objective rate (ORR) ICB RECIST v1.1....
We previously identified a chemotherapy-induced paracrine inflammatory loop that paradoxically mitigates the anti-tumor effect of chemotherapy and triggers metastatic propagation in breast lung cancer models. Therefore, we sought to further validate translate these findings into patient care by coupling anti-TNF-α drug certolizumab pegol with standard cisplatin doublet chemotherapy. Here first anti-metastatic liver-metastatic Lewis Lung Carcinoma model. then evaluate safety, efficacy,...
8014 Background: At the first planned interim analysis of ADRIATIC, consolidation D significantly improved dual primary endpoints overall and progression-free survival (PFS) vs P in patients (pts) with LS-SCLC no progression after cCRT. We assess clinical characteristics, patterns progression, associated molecular biomarkers EPs (pts PFS <6 mos) LTPs (PFS or censored >12 arms. Methods: Pts stage I–III LS-SCLC, WHO performance status (PS) 0/1, cCRT were randomized to (n=264), +...
Transforming growth factor (ß1TGFß1) can promote proliferation in late stage cancers but acts as a tumor suppressor normal epithelial cells and early cancers. Although, the TGFß pathway has been shown to play key role tumorigenesis metastasis, only limited number of models have developed understand this process. Here, we present novel model system discern paradoxical TGFß1 using MDA-MB-231 (MB-231) cell line. The MB-231 triple-negative breast cancer line extensively characterized continue...
9003 Background: Treatment with PD-(L)1 inhibitors is now standard therapy for patients lung cancer. The immunosuppressive effect of steroids may reduce efficacy blockade. On-treatment treatment irAEs do not appear to affect efficacy, but the potential impact baseline at time initiation unknown. Clinical trials typically excluded receiving corticosteroids leading us use real-world data examine initiation. Methods: We identified 640 naïve advanced NSCLC from two institutions (Memorial Sloan...
9034 Background: In patients with RET-rearranged lung cancers, multikinase inhibitors (e.g. cabozantinib and vandetanib) specific pemetrexed-containing) chemotherapy regimens have documented activity. contrast, PD-L1 expression, tumor mutational burden (TMB), the treatment outcomes of immunotherapy are not well characterized in this genomic subset. Methods: Patients a pathologically confirmed diagnosis cancer harboring RET rearrangement were identified between January 2012 December 2017....
TPS9080 Background: SCLC is an aggressive neuroendocrine tumor with poor prognosis and few treatment options. Delta-like ligand 3 (DLL3) inhibitory Notch that highly expressed on the surface of most tumors but minimally in normal tissues. As such, DLL3 may be a promising therapeutic target. AMG 757 HLE BiTE immune therapy designed to redirect cytotoxic T cells cancer by binding CD3 cells, resulting cell activation expansion cell-dependent killing cells. In addition its direct antitumor...
ABSTRACT Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes defined by differential expression of ASCL1 , NEUROD1 and POU2F3 (SCLC-A, -N, -P, respectively), which are associated with distinct therapeutic vulnerabilities. To define the heterogeneity tumors their microenvironments across subtypes, we sequenced 54,523 cellular transcriptomes from 21 human biospecimens. Our single-cell SCLC atlas reveals tumor diversity exceeding adenocarcinoma, driven canonical,...
<h3>Background</h3> Delta-like ligand 3 (DLL3) is an inhibitory Notch that highly expressed in small cell lung cancer (SCLC) and minimally normal tissues.<sup>1</sup> AMG 757, a half-life extended BiTE® immune therapy, binds to DLL3 on tumor cells CD3 T cells, resulting cell-dependent killing of cells. We report initial safety efficacy from the ongoing phase 1 study 757 patients with SCLC. <h3>Methods</h3> was administered intravenously every two weeks (with/without step dose) at doses...
9067 Background: Small cell lung cancer (SCLC) is an aggressive disease, characterized by inevitable chemotherapy resistance and rapid progression. We hypothesized that circulating tumor DNA (ctDNA) analysis can rapidly identify sensitivity to platinum-based therapy. Methods: Patients with SCLC at Memorial Sloan Kettering Cancer Center underwent serial plasma collections, including prior the start of treatment Cycle 2 Day 1 therapy (C2D1). Tumor mutations were identified from pre-treatment...