A5017157410- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Viral-associated cancers and disorders
- Gastric Cancer Management and Outcomes
- Gastrointestinal Tumor Research and Treatment
- Helicobacter pylori-related gastroenterology studies
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Advanced biosensing and bioanalysis techniques
- Radiopharmaceutical Chemistry and Applications
- Synthesis and Biological Evaluation
- Lung Cancer Research Studies
- Click Chemistry and Applications
- Cancer therapeutics and mechanisms
- Brain Metastases and Treatment
- Esophageal Cancer Research and Treatment
- Animal Virus Infections Studies
- Studies on Chitinases and Chitosanases
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Glioma Diagnosis and Treatment
- Immune Cell Function and Interaction
Massachusetts General Hospital
2017-2025
Harvard University
2018-2025
Cygnal Therapeutics (United States)
2019-2022
Dana-Farber Cancer Institute
2012-2022
Center for Cancer Research
2019
Broad Institute
2017
National Cancer Center
2016
Metropolitan State University
2015
Abstract Purpose: Patients with KRAS-mutant non–small cell lung cancer (NSCLC) brain metastases (BM) have a poor prognosis. Adagrasib (MRTX849), potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. has been optimized for favorable pharmacokinetic properties, including long half-life (∼24 hours), extensive tissue distribution, dose-dependent pharmacokinetics, central nervous system penetration; however, BM-specific...
Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab 5-FU/platinum GEA. Using serial biopsy primary tumor at baseline, after one cycle 5-FU/platinum, addition pembrolizumab, transcriptionally profiled 358,067 single cells identify evolving...
Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with poor prognosis and limited treatment options. We present single arm Phase II study of 18 patients LMD receiving combined ipilimumab nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point overall survival at 3 months (OS3). Secondary points include toxicity, cumulative time-to-progression months, progression-free survival. A Simon two-stage design used to compare null...
Abstract Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element overexpressed in carcinomas high-risk precursors during carcinogenesis with negligible expression normal tissues, suggesting ORF1p could...
The CRISPR-Cas9 system has revolutionized gene editing both on single genes and in multiplexed loss-of-function screens, enabling precise genome-scale identification of essential to proliferation survival cancer cells. However, previous studies reported that an anti-proliferative effect Cas9-mediated DNA cleavage confounds such measurement genetic dependency, particularly the setting copy number gain 1-4 . We performed essentiality screens 342 cell lines found this is common all lines,...
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently end stage of the disease. Immune checkpoint inhibitors (ICI) provide a opportunity against MBM; however, MBM tumor microenvironment (TME) has not been fully elucidated in context ICI. To dissect unique elements TME and correlates response to ICI, we collected 32 fresh performed single-cell RNA sequencing T-cell receptor clonotyping on T cells from matched blood...
Esophageal, gastroesophageal junction, and gastric adenocarcinomas, referred to collectively as adenocarcinomas (GEAs), are a major cause of global cancer-related mortality. Our increasing molecular understanding has led the addition biomarker-directed approaches defined subgroups improved survival in selected patients, such those with HER2 Claudin18.2 overexpression. Immune checkpoint inhibitors (ICIs) have revolutionized treatment cancer, including GEA, but biomarkers beyond PD-L1...
452 Background: We performed a single-arm phase II study of neoadjuvant NALIRIFOX and chemoradiation (CRT) with concurrent carboplatin/taxol (C/T) followed by surgery in patients locally advanced gastroesophageal (GE) cancer. Methods: Patients were enrolled on an NCI sponsored, prospective, single arm (NCT04656041). Key eligibility criteria included: histologically confirmed T3/4 or lymph node (LN) positive GE junction esophageal cancer, ECOG PS ≤1, age 18+, life expectancy > 3 months....
TPS505 Background: Diffuse-type gastric cancer (DGC) accounts for approximately one third of diagnoses. DGC is characterized by poor differentiation, discohesive growth, frequent peritoneal spread, chemoresistance, and inferior survival compared to intestinal-type cancer. Moreover, commonly genomically stable often lacks clinically actionable targets such as ERBB2 amplification. Alterations enriched in including loss-of-function CDH1 mutations gain-of-function RHOA can facilitate increased...
470 Background: Gene copy number (CN) amplifications (amps) and/or protein overexpression in ERBB2 , EGFR FGFR2 and MET represent established emerging clinical targets GE. Various methodologies are used to report gene amp or with some data suggesting FISH ratio may predict therapy response. Quantitative methods for NGS CN relationship ISH/IHC remains largely unresolved. We studied the landscape of targetable amps GE understand correlations quantitative outcomes. Methods: tissue (N = 20,468)...
385 Background: The advent of biomarker-driven therapeutic strategies brings increasing precision to the treatment G/GEJ cancer, placing biomarker testing at forefront patient management. management evolving logistics for and related decision-making can be challenging, especially in community clinics. As part a multi-center quality improvement initiative, we evaluated current gaps practice patterns including multidisciplinary care cancers oncology centers. Methods: Between 5/2024 8/2024,...
KRAS G12C mutations are important oncogenic that confer sensitivity to direct inhibitors. We retrospectively identified patients with KRAS+ NSCLC from 2015 2019 and assessed the imaging features of primary tumor distribution metastases compared those non-G12C driven by fusion events (RET, ALK, ROS1) EGFR at time initial diagnosis. Two hundred fifteen (G12C: 83; non-G12C: 132) were included. On single variate analysis, group was more likely than have cavitation (13% vs. 5%, p = 0.04) lung...
DNA is an organic molecule that highly vulnerable to chemical alterations and breaks caused by both internal external factors. Cells possess complex advanced mechanisms, including repair, damage tolerance, cell cycle checkpoints, death pathways, which together minimize the potentially harmful effects of damage. However, in cancer cells, normal tolerance response processes are disrupted or deregulated. This results increased mutagenesis genomic instability within a known driver progression...
Abstract Background In nongastric gastrointestinal (GI) cancers, HER2-positive (HER2+) disease is not common. breast cancer, HER2 status associated with increased risk of brain metastases and response to HER2-targeted therapy. The purpose this project was compare in GI cancer versus matched prior sites order determine if HER2+ more common intracranially. Materials Methods We identified 28 patients who had craniotomy for between 1999 2017 intracranial metastatic tissue available at...
Objective Posterior fossa meningiomas are surgically challenging tumors that associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior meningioma facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing targetable AKT1, SMO, PIK3CA was performed 61 using Illumina NextSeq 500 a target depth >500 × . Samples were further interrogated 53 cancer-relevant...
<div>Abstract<p>Adding anti–programmed cell death protein 1 (anti–PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (<i>n</i> = 47) sequentially adding pembrolizumab 5-FU/platinum GEA. Using serial biopsy primary tumor at baseline, after one cycle 5-FU/platinum, addition pembrolizumab, transcriptionally...
The Cancer Genome Atlas (TCGA) has identified four distinct molecular subtypes of gastric cancer (GC) with prognostic significance: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI)-high, genomically stable (GS), and chromosomal (CIN). Unfortunately, the complex analysis required for TCGA classification limits its practical use in clinical settings. Our study sought to devise a next-generation sequencing (NGS)-based method classify GC more efficiently, serving as promising...