A5002861948- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Lung Cancer Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Research Studies
- Radiopharmaceutical Chemistry and Applications
- PI3K/AKT/mTOR signaling in cancer
- Colorectal Cancer Treatments and Studies
- Medical Imaging Techniques and Applications
- Metastasis and carcinoma case studies
- Trace Elements in Health
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Folate and B Vitamins Research
- Single-cell and spatial transcriptomics
- Genetic factors in colorectal cancer
- Gene Regulatory Network Analysis
- Renal and related cancers
Dana-Farber Cancer Institute
2016-2023
Broad Institute
2019-2022
Harvard University
2018-2021
Oklahoma State University
2021
Oklahoma State University Oklahoma City
2020
University College London
2016
University of London
2016
Universidad de Londres
2016
Dana-Farber Brigham Cancer Center
2016
Brigham and Women's Hospital
2016
Abstract The recent approval of two PD-1 inhibitors for the treatment non–small cell lung cancer (NSCLC) has rapidly led to widespread use these agents in oncology practices. Pneumonitis been recognized as a potentially life-threatening adverse event among NSCLC patients treated with inhibitors; however, detailed clinical and radiographic manifestations this entity remain be described. We report on cases anti–PD-1 pneumonitis advanced nivolumab after its FDA approval. Both presented...
Abstract Assays to study cancer cell responses pharmacologic or genetic perturbations are typically restricted using simple phenotypic readouts such as proliferation rate. Information-rich assays, gene-expression profiling, have generally not permitted efficient profiling of a given perturbation across multiple cellular contexts. Here, we develop MIX-Seq, method for multiplexed transcriptional post-perturbation mixture samples with single-cell resolution, SNP-based computational...
Tumor response characteristics using immune-related RECIST1.1 (irRECIST1.1) in advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab monotherapy the clinical setting have not been previously described a direct comparison assessments according to conventional RECIST1.1.Fifty-six NSCLC after its Food and Drug Administration (FDA) approval were retrospectively studied. burden was quantified on serial CT scans during therapy irRECIST1.1, which uses unidimensional...
MET inhibitors can be effective therapies in patients with exon 14 (METex14) mutant non-small cell lung cancer (NSCLC). However, long-term efficacy is limited by the development of drug resistance. In this study, we characterize acquired amplification wild-type (WT) KRAS as a molecular mechanism behind crizotinib resistance three cases METex14-mutant NSCLC and propose combination therapy to target it.The patient-derived line xenograft (PDX) DFCI358 were established from crizotinib-resistant...
Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for EGFR-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of ERBB family that functions by dimerizing with other members (EGFR and HER2) frequently overexpressed in NSCLC. Although TKI mechanisms do not lead alterations HER3, we hypothesized targeting might improve efficacy...
Abstract Purpose: Evaluating drug responses using primary patient-derived cells ex vivo represents a potentially rapid and efficient approach to screening for new treatment approaches. Here, we sought identify neratinib combinations in HER2 mutant non–small cell lung cancer (NSCLC) patient xenograft-derived organotypic spheroids (XDOTS) short-term system. Experimental Design: We generated two HER2-mutant NSCLC PDX models [DFCI359 (HER2 exon19 755_757LREdelinsRP) DFCI315 exon20...
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...
Journal Article A quantitative systems approach to identify paracrine mechanisms that locally suppress immune response Interleukin-12 in the B16 melanoma model Get access Yogesh M. Kulkarni, Kulkarni Department of Chemical Engineering and Mary Babb Randolph Cancer Center, West Virginia University, P.O. Box 6102, Morgantown, WV 26506, USA. Tel: +1 304-293-9346 Search for other works by this author on: Oxford Academic Google Scholar Emily Chambers, Chambers Microbiology, Immunology Cell...
Combining experiments with mathematical modeling provides insights into the responses of T cells to cytokines.
Prior studies characterized the association of molecular alterations with treatment-specific outcomes in KRAS-mutant (KRAS
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...
We pursued genomic analysis of an exceptional responder with non-small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets.In this open-label, single-arm phase II study (NCT01829217), enriched cohort patients advanced NSCLC was treated the multi-kinase inhibitor sunitinib. The primary endpoint objective response rate. Tissue collected for responders, and candidate oncogene validated using in vitro models edited by CRISPR-Cas9.Of 13 enrolled, 1 patient...
A subset of drug-resistant EGFR -mutant MET -amplified lung cancer switches oncogenic dependence to and is treatable with inhibitor monotherapy.
The SLC39A8 gene encodes a divalent metal transporter, ZIP8. is associated with pleiotropic effects across multiple tissues, including the brain. We determine different brain magnetic resonance imaging (MRI) phenotypes SLC39A8. used phenome-wide association study approach followed by joint and conditional analysis. Using summary statistics datasets from MRI genome-wide on adult United Kingdom (UK) Biobank participants, we systematically selected all single-nucleotide polymorphisms (SNPs)...
9087 Background: KRAS is the most frequently mutated oncogene in NSCLC, and such tumors lack effective targeted therapy. Unlike other activating oncogenes associated with never/light-smokers (NS), mutations are found both smokers. However, relationship between smoking status a KRASm+ tumor’s genomic complexity unclear. Methods: Targeted next generation sequencing (NGS) data at our institution from 7/13-1/16 was reviewed to identify NSCLC tumors. All patients < 10 pack-year (py) history (NS)...
9069 Background: Non-small cell lung cancers (NSCLC) harboring METex14 activating mutations can respond dramatically to treatment with MET TKIs, but the mechanisms of acquired resistance these therapies are not well understood. Methods: We performed next generation sequencing on serial plasma samples and/or tumor biopsies and one autopsy case from patients mutant NSCLC identify type 1 TKI crizotinib 2 glesatinib. Results: Samples 12 were included in this analysis. In 4 cases (33%),...
Abstract Assays to study cancer cell responses pharmacologic or genetic perturbations are typically restricted using simple phenotypic readouts such as proliferation rate the expression of a marker gene. Information-rich assays, gene-expression profiling, generally not amenable efficient profiling given perturbation across multiple cellular contexts. Here, we developed MIX-Seq, method for multiplexed transcriptional post-perturbation mixture samples with single-cell resolution, SNP-based...