A5041842073- Cancer Immunotherapy and Biomarkers
- Sarcoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Colorectal and Anal Carcinomas
- Lymphoma Diagnosis and Treatment
- Vascular Tumors and Angiosarcomas
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- Vitamin D Research Studies
- Immune cells in cancer
- Cancer Cells and Metastasis
- Chromosomal and Genetic Variations
- Cancer Diagnosis and Treatment
- Cardiac tumors and thrombi
- Neuroblastoma Research and Treatments
- Multiple Myeloma Research and Treatments
- Bioinformatics and Genomic Networks
- PARP inhibition in cancer therapy
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
Memorial Sloan Kettering Cancer Center
2010-2025
Cornell University
2022-2024
Kettering University
2020-2024
University of California, San Diego
2007-2012
Ludwig Cancer Research
2012
Ludwig Cancer Research
2011-2012
Coronavirus-2019 (COVID-19) mortality is higher in patients with cancer than the general population, yet cancer-associated risk factors for COVID-19 adverse outcomes are not fully characterized.
Abstract The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification therapeutic targets, research, advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or few subtypes. Herein, we report comparative analysis 2,138 representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable...
Data from large-scale protein interaction screens for humans and model eukaryotes have been invaluable developing systems-level models of biological processes. Despite this value, only a limited amount data is available prokaryotes. Here we report the systematic identification interactions bacterium Campylobacter jejuni, food-borne pathogen major cause gastroenteritis worldwide. Using high-throughput yeast two-hybrid detected reproduced 11,687 interactions. The resulting map includes 80%...
Abstract Purpose: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor, proposed to shift the tumor microenvironment toward immune-stimulated state, showed early promise in melanoma but has not been studied sarcoma. This study combined epacadostat with pembrolizumab, which modest activity select sarcoma subtypes. Patients and Methods: phase II enrolled patients advanced into five cohorts including (i) undifferentiated pleomorphic (UPS)/myxofibrosarcoma, (ii) liposarcoma (LPS), (iii)...
Background Angiosarcoma is a histologically and molecularly heterogeneous vascular neoplasm with aggressive clinical behavior. Emerging data suggests that immune checkpoint blockade (ICB) efficacious against some angiosarcomas, particularly cutaneous angiosarcoma of the head neck (CHN). Methods Patients confirmed treated ICB-based therapy at comprehensive cancer center were retrospectively identified. Clinical characteristics results targeted exome sequencing, transcriptome...
Abstract PD-1 blockade (nivolumab) efficacy remains modest for metastatic sarcoma. In this paper, we present an open-label, non-randomized, non-comparative pilot study of bempegaldesleukin, a CD122-preferential interleukin-2 pathway agonist, with nivolumab in refractory sarcoma at Memorial Sloan Kettering/MD Anderson Cancer Centers (NCT03282344). We report on the primary outcome objective response rate (ORR) and secondary endpoints toxicity, clinical benefit, progression-free survival,...
Ty elements are high copy number, dispersed repeated sequences in the Saccharomyces cerevisiae genome known to mediate gross chromosomal rearrangements (GCRs). Here we found that introduction of Ty912, a previously identified Ty1 element, onto non-essential terminal region left arm chromosome V led 380-fold increase rate accumulating GCRs wild-type strain. A survey 48 different mutations those either increased or decreased Ty-mediated and demonstrated suppression differs from both low repeat...
The link between the "stress phenotype"-a well-established hallmark of cancer-and its role in tumor progression and intratumor heterogeneity remains poorly defined. integrated stress response (ISR) is a key adaptive pathway that enables survival under oncogenic stress. While ISR has been implicated promoting growth, precise driving evolution not elucidated. In this study, using genetically engineered mouse models, we demonstrate activation-indicated by elevated levels phosphorylated eIF2...
Unbiased forward genetic screens for mutations causing increased gross chromosomal rearrangement (GCR) rates in Saccharomyces cerevisiae are hampered by the difficulty reliably using qualitative GCR assays to detect mutants with small but significantly rates. We therefore developed a bioinformatic procedure genome-wide functional genomics identify and prioritize candidate GCR-suppressing genes on basis of shared drug sensitivity suppression similar interactions as known suppressors. The...
Abstract Purpose: Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes its antitumor effects. Therefore, we hypothesized combination lenvatinib pembrolizumab would lead improved clinical outcomes in sarcoma. Patients Methods: This was...
Abstract The association between immune-related AEs (irAE) and outcome in patients with sarcoma is not known. We retrospectively reviewed a cohort of advanced treated immune checkpoint blockade (ICB)-based therapy. Association irAEs survival was assessed using Cox regression model that incorporated irAE occurrence as time-dependent covariate. Tumor samples available RNA sequencing data were stratified by presence an to identify patterns differential gene expression. A total 131 included....
Programmed cell death protein 1 (PD-1) blockade can mediate objective responses in advanced sarcomas, but their durability has not been established and it is unclear if hyperprogressive disease (HPD) occurs sarcomas treated with PD-1 inhibitors.
TPS2690 Background: Identifying novel approaches that harness and augment anti-tumor immune responses represents an important area of ongoing research drug development. Stimulator interferon genes (STING) is endoplasmic protein receptor acts as innate mediator by generating protective type 1 interferons when cytosolic DNA detected in cells. STING also channels protons across golgi membranes promoting autophagy pyroptosis. CRD3874-SI a first class small molecule allosteric agonist potent...
Abstract Genetically engineered mouse models (GEMM) of cancer are a useful tool for exploring the development and biological composition human tumors and, when combined with single-cell RNA-sequencing (scRNA-seq), provide transcriptomic snapshot data to explore heterogeneity cell states in an immunocompetent context. However, cross-species comparison often suffers from batch effect inherent differences between mice humans decreases signal insights that can be gleaned these models. Here, we...
Aneuploidy and gross chromosomal rearrangements (GCRs) can lead to genetic diseases the development of cancer. We previously demonstrated that introduction repetitive retrotransposon Ty912 onto a nonessential chromosome arm Saccharomyces cerevisiae led increased genome instability predominantly due rates formation monocentric nonreciprocal translocations. In this study, we adapted Multiplex Ligation–dependent Probe Amplification (MLPA) analyze large numbers these GCRs. Using MLPA, found...
11549 Background: Select sarcomas are infiltrated with immunosuppressive myeloid cells. DCC-3014 is an inhibitor of the CSF1R kinase that decreases tumor infiltrating cells in preclinical models. We hypothesized combined anti-PDL1 avelumab would be safe and tolerable, decrease cells, increase cytotoxic T Methods: This investigator initiated, open label, single center, phase I study plus patients (pts) unresectable or metastatic sarcoma utilized a standard 3+3 dose escalation design. was...
11518 Background: GD is an alternative to doxorubicin in the front line setting advanced STS. In Phase I portion of this study, PD-1 antibody R, plus GD, was generally well tolerated. We hypothesized that R+GD would be more effective than historical controls treated with alone. Methods: This ongoing open-label single-center study pts treatment-naïve unresectable or metastatic high-grade G (900 mg/m 2 ) administered on days 1 and 8 D (75 day 8, 21-day cycles. R (375 mg flat dose) starting...
11516 Background: In a phase III trial, GD had similar response and survival rates to doxorubicin when administered as first-line therapy advanced STS pts. G D have each demonstrated synergy with PD-1 blockade in pre-clinical or clinical studies. We hypothesized that plus R would be safe, tolerable, synergistic activity STS. Methods: This is an ongoing open-label, single-center, I/II trial of (INCMGA00012) combined pts treatment-naïve unresectable metastatic high-grade Herein, we report the...
ABSTRACT Response to immune checkpoint inhibition (ICI) in sarcoma is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy patient selection. One potential mechanism epigenetic de-repression transposable elements (TEs), which stimulates antitumor immunity. Here, we used transcriptomic data assign immune-hot versus immune-cold status 67 pre-treatment biopsies sarcomas from patients treated on trials. Progression-free survival response was superior the...