A5009070223- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- Botulinum Toxin and Related Neurological Disorders
- PI3K/AKT/mTOR signaling in cancer
- Ovarian cancer diagnosis and treatment
- Clostridium difficile and Clostridium perfringens research
- Glycosylation and Glycoproteins Research
- Renal cell carcinoma treatment
- Lung Cancer Treatments and Mutations
- Biochemical and Molecular Research
- Histiocytic Disorders and Treatments
- Chromatin Remodeling and Cancer
- MRI in cancer diagnosis
- Peptidase Inhibition and Analysis
- Bacterial Identification and Susceptibility Testing
- Cell Image Analysis Techniques
- Chronic Lymphocytic Leukemia Research
- Radiomics and Machine Learning in Medical Imaging
- Sarcoma Diagnosis and Treatment
- Vascular Malformations and Hemangiomas
- Advanced Breast Cancer Therapies
Memorial Sloan Kettering Cancer Center
2010-2024
Cornell University
2017-2023
Kettering University
2017-2019
State University of New York
2000
<h3>Importance</h3> The histiocytic neoplasms Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are highly enriched for<i>BRAF</i>V600 mutations have been previously shown to be responsive treatment with vemurafenib, an inhibitor of the BRAF V600 kinase. However, long-term efficacy safety prolonged vemurafenib use in these patients not defined. Here we analyze final data for ECD LCH enrolled VE-BASKET study. <h3>Objective</h3> To determine adults or <h3>Design, Setting,...
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity AKT inhibition AKT-mutant cancers. Patients Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary points progression-free survival (PFS) response according Response Evaluation Criteria Solid Tumors (RECIST)....
Abstract NRG1 rearrangements are recurrent oncogenic drivers in solid tumors. binds to HER3, leading heterodimerization with other HER/ERBB kinases, increased downstream signaling, and tumorigenesis. Targeting ERBBs, therefore, represents a therapeutic strategy for these cancers. We investigated zenocutuzumab (Zeno; MCLA-128), an antibody-dependent cellular cytotoxicity–enhanced anti-HER2xHER3 bispecific antibody, fusion–positive isogenic patient-derived cell lines xenograft models. Zeno...
Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response animals, which warrants clinical investigation.This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection across 6 dose cohorts (1 × 104 3 106 spores, 3+3 dose-escalation design)...
Background PI3K pathway activation is common in endometrial cancer. We evaluated the safety and efficacy of dual PI3K/mTOR inhibitor, LY3023414, patients with advanced cancer harboring activating mutations pathway. Methods conducted a single‐arm phase 2 study monotherapy LY3023414. Eligible had any grade, prior management 1‐4 cytotoxic lines, prospectively defined as loss‐of‐function PTEN alteration or PIK3CA , AKT1 PIK3R1 PIK3R2 MTOR . The primary objective was best overall response rate...
Background Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed the majority of OCs and presents an attractive target for a combination immunotherapy potentially overcome resistance ICI OCs. The current study sought examine clinical immunologic responses TPIV200, multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab patients platinum-resistant...
Imaging reports that consistently document all disease sites with a potential to increase surgical complexity or morbidity can facilitate ovarian cancer treatment planning.
Abstract Background: NRG1 fusions are oncogenic drivers of various cancers including pancreatic and lung adenocarcinomas. fusion proteins bind to HER3, leading HER2/HER3 heterodimerization, increased downstream signaling, tumor growth. MCLA-128 is a bispecific antibody directed against HER2 HER3 that docks on blocks ligand binding thereby preventing signaling. In contrast tyrosine kinase inhibitors or anti-HER3 monoclonal antibodies, was shown in vitro vivo potently inhibit ligand-driven...
Abstract Background: Somatic HER2 (ERBB2) and HER3 (ERBB3) mutations can lead to constitutive activation in the absence of gene amplification. They occur a variety solid tumors with prevalence that does not exceed 5-10% any tumor type. Activating receptor extracellular transmembrane domains, at multiple hotspots kinase domain, no single mutation predominating. Neratinib, an irreversible pan-HER tyrosine inhibitor, inhibits growth HER2- HER3-mutant preclinical models. We explored clinical...
Abstract Purpose: Even though BRAF fusions are increasingly detected in standard multigene next-generation sequencing panels, few reports have explored their structure and impact on clinical course. Experimental Design: We collected data from patients with fusion–positive cancers identified through a genotyping protocol of 97,024 samples. Fusions were characterized reviewed for oncogenic potential (in-frame status, non-BRAF partner gene, intact kinase domain). Results: found 241 tumors 212...
<p>Supplemental Figure 5. Oncoprint for de novo BRAF fusions (≥10%) most common histologies.</p>
<p>Supplemental Figure 4. Oncoprint for de novo BRAF fusions.</p>
<p>Supplemental Figure 6. Oncoprint for acquired BRAF fusions.</p>
<p>Supplemental Figure 1. Consort Diagram.</p>
<p>Supplemental Table 4. Treatments prior to identification of acquired BRAF fusions.</p>
<p>Supplemental Table 1. Baseline characteristics of patients with de novo and acquired BRAF fusions.</p>
<p>Supplemental Table 3: Baseline characteristics of patients with de novo BRAF fusions treated MAPK-pathway directed therapies.</p>
<div>AbstractPurpose:<p>Even though <i>BRAF</i> fusions are increasingly detected in standard multigene next-generation sequencing panels, few reports have explored their structure and impact on clinical course.</p>Experimental Design:<p>We collected data from patients with fusion–positive cancers identified through a genotyping protocol of 97,024 samples. Fusions were characterized reviewed for oncogenic potential (in-frame status,...
<p>Supplemental Figure 3. Structures of top 13 most common BRAF fusion isoforms.</p>