A5055915497- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Gastric Cancer Management and Outcomes
- Cholangiocarcinoma and Gallbladder Cancer Studies
- PARP inhibition in cancer therapy
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Neutropenia and Cancer Infections
- Colorectal and Anal Carcinomas
- Wnt/β-catenin signaling in development and cancer
- Cancer Treatment and Pharmacology
- Cancer-related gene regulation
- Cancer, Lipids, and Metabolism
- HER2/EGFR in Cancer Research
- DNA Repair Mechanisms
- Sarcoma Diagnosis and Treatment
- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
Georgetown University Medical Center
2016-2025
Georgetown University
2016-2025
MedStar Georgetown University Hospital
2012-2025
Georgetown Lombardi Comprehensive Cancer Center
2017-2024
Vince Lombardi Cancer Clinic
2023-2024
Caris Life Sciences (United States)
2023
Methodist Hospital
2023
University of Kansas Medical Center
2023
MedStar Washington Hospital Center
2022
St. Vincent's University Hospital
2022
The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, PD-L1 expression determine their interrelationship in Here, a total 4,125 tumors from 14 cancer sites were studied using validated assays. Next-generation sequencing was performed on genomic...
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those left-sided or rectal cancers, these patient subgroups respond differently to biological therapies. Historically, management metastatic been similar, cancer grouped together large clinical trials. Clearly, differences molecular biology among colon, should be further...
Biliary tract cancers (BTCs) are a heterogeneous group of aggressive, rare malignancies with limited standard chemotherapeutic options for advanced disease. Recent studies have demonstrated potential novel biliary cancer targets and possible role immunotherapy in the treatment patients this Intrahepatic cholangiocarcinoma (IHCC), extrahepatic (EHCC), gallbladder carcinoma (GBC) frequently grouped together clinical trials despite differences tumor biology.To further investigate biology...
KRAS mutation (MT) is a major oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). A small subset of PDACs harbor wild-type (WT). We aim to characterize the molecular profiles WT PDAC uncover new pathogenic drivers and offer targeted treatments.
Neuregulin 1 (NRG1) fusions are recurrent oncogenic drivers found in multiple solid tumors. NRG1 binds to human epidermal growth factor receptor 3 (HER3), leading heterodimerization with HER2 and activation of downstream proliferation pathways. The efficacy safety zenocutuzumab, a bispecific antibody against HER3, patients fusion-positive tumors unclear. In this registrational, phase 2 clinical study, we assigned advanced cancer involving any tumor type receive zenocutuzumab at dose 750 mg...
105 Background: NRG1 fusions are rare oncogenic drivers that have been identified in a variety of solid tumors. These proteins bind HER3, leading to HER2/HER3 heterodimerization and transformation. Zenocutuzumab (MCLA-128; Zeno) is Biclonics antibody overcomes HER3 mediated (or fusion) signaling tumor cells. Zeno docks on HER2, then binds blocks the fusion-HER3 interaction with HER2. being evaluated patients (pts) NRG1+ cancer ongoing pivotal phase 2 part eNRGy study early access program...
2538 Background: BDC-1001 is a HER2-targeted immune-stimulating antibody conjugate (ISAC), designed to trigger local activation of the innate immune system and generate durable tumor-targeted adaptive response. incorporates trastuzumab biosimilar (EG12014) conjugated proprietary TLR7/8 agonist using non-cleavable linker cell membrane-impermeable payload. An international phase 1/2 study was initiated evaluate safety ± nivolumab (nivo) identify recommended 2 dose (RP2D) considering PK/PD...
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis part of remodeling and sought to characterize pathways leading in IPF. found diameter lymphatic vessels alveolar spaces IPF tissue correlated with severity, suggesting microenvironment plays role lymphangiogenic process. bronchoalveolar lavage fluid (BALF) from...
Background: Patients with biliary tract cancer (BTC) have a dismal prognosis and limited treatment options. Given the potential for immunotherapy in patients BTC, we studied expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) evaluated associated genetic alterations BTC. Methods: By immunohistochemistry (IHC), PD-L1 (SP142 antibody; ≥2+ and/or ≥5% staining on tumor cells considered positive) PD-1 [NAT105 ≥1+ infiltrating lymphocytes (TILs) positive] was next-generation...
3003 Background: NRG1 fusion proteins are oncogenic drivers in pancreas cancer and other solid tumors. They bind HER3, leading to HER2/HER3 heterodimerization transformation. The activity of zenocutuzumab (MCLA-128; zeno), a bispecific antibody targeting signaling positive ( NRG1+) cancers, is being evaluated the ongoing global multicenter phase 2 part eNRGy study early access program (EAP). Methods: Enrolled patients (pts) have advanced NRG1+ cancer, non-small cell lung (NSCLC), tumors...
Abstract Background FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or avelumab (anti-PD-L1) CEA-targeted vaccine. Methods Patients with untreated MSS mCRC enrolled lead-in arm assessing safety + immuno-oncology agents (IO). Next, were IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters analyzed. Results Six lead-in, 10 SOC,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) of the head (H) and body/tail (B/T) differ in embryonic origin, cell composition, blood supply, lymphatic venous drainage, innervation. We aimed to compare molecular tumor immune microenvironment (TIME) profiles PDAC H vs. B/T. A total 3499 samples were analyzed via next-generation sequencing (NGS) RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), immunohistochemistry (Caris Life Sciences,...
The incidence of colorectal cancer (CRC) in younger patients is rising, mostly due to tumors the descending colon and rectum. Therefore, we aimed explore molecular differences left-sided CRC between (≤45 years) older (≥65).In total, 1,126 tumor samples from splenic flexure (and including) rectum were examined by next-generation sequencing (NGS), immunohistochemistry, situ hybridization. Microsatellite instability (MSI) mutational burden (TMB) assessed NGS.Younger (n = 350), when compared...
Neuregulin 1 (NRG1) fusions, which activate ErbB signaling, are rare oncogenic drivers in multiple tumor types. Afatinib is a pan-ErbB family inhibitor that may be an effective treatment for NRG1 fusion-driven tumors.
Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and associated with chemosensitivity. Although the mismatch repair system has been extensively studied, clinical implications other mechanisms DDR alterations in patients colorectal remain unclear. This study aimed understand pathways their association common features cancer.Next-generation sequencing whole-transcriptome were conducted using formalin-fixed paraffin-embedded samples submitted commercial...
Abstract Purpose: Gene fusions involving R-spondin (RSPOfp) and RNF43 mutations have been shown to drive Wnt-dependent tumor initiation in colorectal cancer. Herein, we aimed characterize the molecular features of RSPOfp/RNF43 mutated (mut) compared with wild-type (WT) cancers gain insights into potential rationales for therapeutic strategies. Experimental Design: A discovery cohort was classified status using DNA/RNA sequencing IHC. An independent used validate our findings. Results: The...
3514 Background: Despite the fundamental role of WNT signaling in GI cancers, especially colorectal cancer (CRC), no drug targeting has been successfully developed. CGX1321, a highly-potent and selective inhibitor O-acyltransferase Porcupine, blocks ligand secretion. Preclinical studies show that CGX1321 inhibits growth tumors with RSPO fusions or inactivating RNF43 mutations. Activation associated immune-suppression resistance to immunotherapy. Methods: The first-in-human trials...
The C-C motif chemokine receptor 5 (CCR5)/C-C ligand (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with CCR5/CCL5 expression CRC and determine whether levels could impact treatment outcomes. 7604 CRCs tested NextGen Sequencing on DNA RNA were analyzed. Molecular evaluated according CCR5 CCL5 tumor gene quartiles. outcomes was assessed two cohorts, including 6341 real-world patients 429 from Cancer Leukemia Group B...
Up to 17% of patients with pancreatic ductal adenocarcinoma (PDAC) harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as
Abstract Purpose: Mutations in KRAS/NRAS (RAS) predict lack of anti-EGFR efficacy metastatic colorectal cancer (mCRC). However, it is unclear if all RAS mutations have similar impact, and atypical beyond those standard guidelines exist. Experimental Design: We reviewed 7 tissue 1 cell-free DNA cohorts 9,485 patients to characterize variants. Using an vitro cell-based assay (functional annotation for treatment), Ba/F3 transformation, vivo xenograft models transduced isogenic clones, we...