Emily E. Van Seventer
A5064958509- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Gastric Cancer Management and Outcomes
- Fibroblast Growth Factor Research
- Lung Cancer Treatments and Mutations
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal Cancer Surgical Treatments
- Cancer Immunotherapy and Biomarkers
- Nutrition and Health in Aging
- Radiomics and Machine Learning in Medical Imaging
- Gastrointestinal Tumor Research and Treatment
- Cancer Research and Treatments
- Cancer survivorship and care
- Multiple and Secondary Primary Cancers
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Metastasis and carcinoma case studies
- Eosinophilic Disorders and Syndromes
- Frailty in Older Adults
- Cytomegalovirus and herpesvirus research
- Cancer Diagnosis and Treatment
- Neuroendocrine Tumor Research Advances
- Viral-associated cancers and disorders
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Broad Institute
2018
National Institute of Allergy and Infectious Diseases
2017
National Institutes of Health
2017
Abstract Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients metastatic melanoma, but the common mechanisms of primary and acquired resistance these agents remain incompletely characterized have yet be validated large cohorts. By analyzing longitudinal tumor biopsies from 17 melanoma treated CPB therapies, we observed point mutations, deletions or loss heterozygosity (LOH) beta-2-microglobulin ( B2M ), an essential component MHC class I...
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy patients with FGFR2 fusion-positive ICC a phase II trial, but durability of response was limited some patients. Here, we report molecular basis for acquired resistance to three via integrative genomic characterization cell-free circulating tumor DNA (cfDNA), primary...
Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA patients with advanced PDAC. Therapeutically genomic alterations were identified 48% (34/71) pathogenic/likely pathogenic germline 18% (13/71) of patients. Overall, 30% (21/71) enrolled experienced change management as result data. Twenty-six had and/or...
Abstract ATP-competitive fibroblast growth factor receptor (FGFR) kinase inhibitors, including BGJ398 and Debio 1347, show antitumor activity in patients with intrahepatic cholangiocarcinoma (ICC) harboring activating FGFR2 gene fusions. Unfortunately, acquired resistance develops is often associated the emergence of secondary domain mutations. Here, we report that irreversible pan-FGFR inhibitor TAS-120 demonstrated efficacy 4 fusion–positive ICC who developed to or 1347. Examination serial...
Abstract Purpose: Detection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery can identify patients with minimal residual disease (MRD) who will ultimately recur. Most ctDNA MRD assays require sequencing to tumor-derived mutations facilitate detection, requiring and blood. We evaluated a plasma-only assay integrating genomic epigenomic cancer signatures enable tumor-uninformed detection. Experimental Design: A total 252 prospective serial plasma specimens from 103...
Abstract While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in V600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 trial of combined PD-1, sparatlizumab (PDR001), dabrafenib trametinib 37 patients CRC. The primary end point was overall rate, secondary points were...
While mutations in BRAF metastatic colorectal cancer (mCRC) most commonly occur at the V600 amino acid, with advent of next-generation sequencing, non-V600 are increasingly identified clinical practice. It is unclear whether these mutants, like V600E, confer resistance to anti-EGFR therapy.We conducted a multicenter pooled analysis consecutive patients BRAF-mutated mCRCs between 2010 and 2017. Non-V600 were divided into functional classes based on signaling mechanism kinase activity:...
ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change early after therapy initiation can predict treatment response and progression-free survival (PFS) patients with metastatic gastrointestinal cancer.A total of 138 cancers tumor profiling by next-generation sequencing had serial blood draws pretreatment at scheduled intervals during therapy. was assessed using individualized droplet digital PCR...
Abstract Purpose: Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiotherapy (CRT) are incompletely characterized. Experimental Design: We performed integrated whole-exome/transcriptome sequencing immune infiltrate analysis on rectal adenocarcinoma tumors prior neoadjuvant CRT (pre-CRT) at time of resection (post-CRT) in 17 patients [8 complete/partial responders, 9 nonresponders (NR)]. Results: was not increased tumor mutational...
Abstract Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance repeat activity cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities these elements preclinical models with preferential effect p53-mutant cell lines linked direct binding p53 to elements. translate findings human phase II trial single-agent treatment metastatic demonstration clinical benefit...
Abstract Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted cell-free DNA (cfDNA) from patients BRAFV600E colorectal cancer receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving resistance, as many eight single patient. We developed pooled clone system to study clonal outgrowth during vitro vivo. In vitro, the dynamics individual...
This study was designed to assess the ability of perioperative circulating tumor DNA (ctDNA) predict surgical outcome and recurrence following neoadjuvant chemoradiation for locally advanced rectal cancer (LARC).Twenty-nine patients with newly diagnosed LARC treated between January 2014 February 2018 were enrolled. Patients received long-course prior surgery. Plasma ctDNA collected at baseline, preoperatively, postoperatively. Next-generation sequencing used identify mutations in primary...
3514 Background: mCRC remains a lethal cancer and immunotherapy in MSS has yet to show significant activity. In preclinical models, radiation induced cellular damage may increase responsiveness via the abscopal effect, with evidence for synergy between therapy (RT) dual checkpoint blockade. this study, we assessed blockade of CTLA-4 PD-1 combined RT as strategy stimulate an immune response patients mCRC. Methods: open-label, single arm phase-2 enrolled 40 (pts). Eligible pts had...
Early-onset colorectal cancer (EOCRC), defined as a diagnosis under age 50, is an emerging public health burden. As many of these individuals fall outside screening guidelines, the development minimally invasive, accurate modality for this population warranted. We evaluated FDA-approved blood-based biomarker methylated Septin9 (mSEPT9) test tool EOCRC. EOCRC plasma, healthy and serum-free conditioned media from cell lines were collected. Cell-free DNA (cfDNA) was isolated bisulfite converted...
Introduction Up to 60% of adults with metastatic colorectal cancer (mCRC) receiving combination cytotoxic chemotherapy may experience loss skeletal muscle mass and function. This study explores associations artificial intelligence (AI)-based assessment hematologic toxicity relative dose intensity (RDI) in mCRC standard chemotherapy. Methods We conducted a retrospective analysis first-line FOLFOX or FOLFIRI over 6 months (≤12 cycles) from 1/2011 11/2018. used validated AI-based on baseline...
Third-generation epidermal growth factor receptor (EGFR) inhibitors like nazartinib are active against EGFR mutation-positive lung cancers with T790M-mediated acquired resistance to initial anti-EGFR treatment, but some patients have mixed responses.Multiple serial tumor and liquid biopsies were obtained from two before, during, after treatment nazartinib. Next-generation sequencing droplet digital polymerase chain reaction performed assess heterogeneity clonal dynamics.We observed the...
Survival in patients with metastatic colorectal cancer (mCRC) has been associated tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival.We performed an observational cohort study, prospectively enrolling receiving chemotherapy for mCRC. retrospectively assessed changes (using computed tomography) weight, each dichotomized as >5% or ≤5% at 3, 6, 12 months after diagnosis used regression models assess...
Colorectal cancer (CRC) incidence in patients younger than 50 years of age, commonly defined as early-onset (EO-CRC), is rising. EO-CRC often presents with distinct clinicopathologic features. However, data on prognosis are conflicting and outcomes modern treatment approaches for metastatic disease still limited.We prospectively enrolled CRC (mCRC) to a biobanking clinical collection protocol from 2014 2018. We grouped the cohort based age at initial diagnosis: < 40 years, 40-49 ≥ years....
Patient-reported outcomes (PROs), such as quality of life (QOL) and symptoms, are often associated with clinical in patients cancer. In practice, oncologists use serum tumor markers (TMs) (ie, carcinoembryonic antigen [CEA] carbohydrate 19-9 [CA 19-9]) imaging to monitor gastrointestinal
3602 Background: ctDNA identifies patients (pts) at high risk for disease recurrence post CRC resection (post-op). Current residual detection approaches assess only genomic alterations (alts) and rely on tissue sequencing to identify tumor-derived alts. We evaluated a plasma-only assay pts. Methods: 72 pts (surgery = 42; adjuvant therapy (adj) 30) had post-op and/or post-adj plasma samples (3-4mL). Extracted cfDNA (median 27 ng) was analyzed using single-sample NGS test validated in early...