A5003320854- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Genetic factors in colorectal cancer
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- Colorectal Cancer Treatments and Studies
- Testicular diseases and treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Genetics, Bioinformatics, and Biomedical Research
- Chromatin Remodeling and Cancer
- PI3K/AKT/mTOR signaling in cancer
- Gastric Cancer Management and Outcomes
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Amino Acid Enzymes and Metabolism
- Gene expression and cancer classification
- Renal cell carcinoma treatment
- Cancer-related molecular mechanisms research
- Pancreatic and Hepatic Oncology Research
Memorial Sloan Kettering Cancer Center
2014-2023
Molecular Oncology (United States)
2018-2023
Kettering University
2018-2023
Cornell University
2016-2017
Ollscoil na Gaillimhe – University of Galway
2012-2016
National University of Ireland
2014
Middle East Technical University
2009
University College Cork
2008-2009
Cancer spread to the central nervous system (CNS) often is diagnosed late and unresponsive therapy. Mechanisms of tumor dissemination evolution within CNS are largely unknown because limited access tissue.We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture 53 patients with suspected or known involvement by cancer.We detected high-confidence somatic alterations 63% (20 32) metastases solid tumors, 50% (six 12)...
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 Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 IDH2, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with IDH1- IDH2-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance inhibition are poorly understood. Here, we describe four cases identify mutant isoform switching,...
Abstract HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor activation and has activity -mutant tumours. SUMMIT is open-label, single-arm, multi-cohort, phase 2, ‘basket’ trial of neratinib patients solid tumours harbouring oncogenic somatic (ClinicalTrials.gov: NCT01953926). The primary objective the BTC cohort, which now complete, first response rate (ORR)...
Abstract HER2 mutations define a subset of metastatic breast cancers with unique mechanism oncogenic addiction to signaling. We explored activity the irreversible pan-HER kinase inhibitor neratinib, alone or fulvestrant, in 81 patients HER2-mutant cancer. Overall response rate was similar without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration appeared longer ER+ receiving combination therapy, although study not designed for direct comparison....
Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal carcinoma (ncRCC) compared with clear (RCC) supports the study combination regimens. We evaluated efficacy everolimus plus bevacizumab patients metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive received 10 mg oral once per day mg/kg intravenously every 2 weeks. primary end point was progression-free survival (PFS) at 6 months. Correlative analyses...
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...
Fibroblast growth factor receptor (FGFR) 2 alterations, present in 5%-15% of intrahepatic cholangiocarcinomas (IHC), are targets FGFR-directed therapies. Acquired resistance is common among patients who respond. Biopsies at the time acquired to targeted agents may not always be feasible and capture genetic heterogeneity that could exist within a patient. We studied circulating tumor DNA (ctDNA) as less invasive means potentially identifying genomic mechanisms FGFR-targeted
Abstract Background Cell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability detect somatic in plasma depends on both assay sensitivity and the fraction of circulating that tumor-derived (i.e., cfDNA tumor fraction). We hypothesized could inform interpretation negative results choice subsequent assays greater genomic breadth or depth. Methods Plasma samples collected from 118 metastatic patients were analyzed with...
Maternal folate levels and polymorphisms in folate-related genes are known risk factors for neural tube defects (NTDs). SNPs the mitochondrial gene MTHFD1L associated with of NTDs. We investigated whether different alleles SNP rs7646 3' UTR can be differentially regulated by microRNAs affecting expression. previously reported that miR-9 targets now we identify miR-197 as an additional miRNA regulator. Both these miRNAs have predicted binding sites region containing rs7646. determined (A/G)...
Although primary germ cell tumors (GCTs) have been extensively characterized, molecular analysis of metastatic sites has limited. We performed whole-exome sequencing and targeted next-generation on paired GCT samples in a patient cohort enriched for cisplatin-resistant disease.Tissue was 100 tumor specimens from 50 patients with GCT, plasma cell-free DNA subset patients.The mutational landscape pairs highly discordant (68% all somatic mutations were discordant). Whereas genome duplication...
4096 Background: FGFR2 alterations are present in 14% of cholangiocarcinomas (CCA) and promising targets investigational FGFR-directed therapies. Cell-free DNA profiling has emerged as a non-invasive approach to monitor disease longitudinally characterize tumor evolution. We describe the use circulating (ctDNA) among patients (pts) with FGFR2-altered CCA receiving FGFR-targeted therapy identification acquired mutations (mut) at resistance. Methods: Serial blood samples were collected from 8...