A5000933337- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Chronic Lymphocytic Leukemia Research
- Colorectal Cancer Treatments and Studies
- Lymphoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Immunotherapy and Biomarkers
- Neuroblastoma Research and Treatments
- Gastric Cancer Management and Outcomes
- Viral-associated cancers and disorders
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer therapeutics and mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Angiogenesis and VEGF in Cancer
Scripps Clinic
2015-2025
Scripps MD Anderson Cancer Center
2016-2023
Scripps Health
2008-2023
Scripps Clinic Medical Group
2010-2020
Scripps Green Hospital
2019-2020
Beth Israel Deaconess Medical Center
2017
Cancer Research Center
2017
Johns Hopkins University
2017
Palmetto Hematology Oncology
2010-2017
Fred Hutch Cancer Center
2017
Purpose Metastatic pancreatic ductal adenocarcinoma is characterized by excessive hyaluronan (HA) accumulation in the tumor microenvironment, elevating interstitial pressure and impairing perfusion. Preclinical studies demonstrated pegvorhyaluronidase alfa (PEGPH20) degrades HA, thereby increasing drug delivery. Patients Methods with previously untreated metastatic were randomly assigned to treatment PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) or (AG). Tumor HA levels measured...
To evaluate the efficacy and safety of pegvorhyaluronidase alfa (PEGPH20) plus nab-paclitaxel/gemcitabine (AG) in patients with hyaluronan-high metastatic pancreatic ductal adenocarcinoma (PDA).HALO 109-301 was a phase III, randomized, double-blind, placebo-controlled study. Patients ≥ 18 years age untreated, metastatic, PDA were randomly assigned 2:1 to PEGPH20 AG or placebo AG. Treatment administered intravenously 4-week cycles (3 weeks on, 1 week off) until progression intolerable adverse...
TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus patients with previously untreated, locally advanced or metastatic pancreatic cancer.
638 Background: HA is a major component of the tumor microenvironment (TME) in PDA. PEGPH20 degrades HA, remodeling TME. In PDA models, has shown antitumor activity and increased TME delivery anticancer agents to improve efficacy. A randomized phase 2 study showed promising results for PEGPH20+AG (PAG) mPDA identified accumulation as biomarker. We present from 3 (NCT02715804) PAG pts with HA-high mPDA. Methods: Pts ≥18 years untreated were (stratified by geographic region) 2:1 or placebo+AG...
Abstract Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving ablation followed by hematopoietic stem cell transplantation multiple myeloma acute myeloid...
CGP results from >60,000 cases were screened to identify NTRK fusion events of neuroendocrine tumors. 2417 NET patients diverse anatomic sites identified. From this dataset, six harbored fusions which included intra- and inter-chromosomal translocations. A frequency approximately 0.3% was found across all subtypes NETs. Three involved translocations NTRK1 with unique partners (GPATCH4, PIP5K1A, CCDC19). Co-occurring alterations occurred in five cases. identified nearly the full spectrum...
Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, 3, encode proteins TRKA, TRKB, TRKC, respectively, involved normal nerve development. Because NETs develop from diffuse system, we sought to determine whether NTRK alterations occur TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely small intestine,...
4008 Background: Hyaluronan (HA) accumulation in the tumor microenvironment produces elevated pressure, vascular compression, and reduced drug delivery. PEGPH20 degrades HA, increasing access therapeutic index of anticancer agents. Methods: In Stage 1 this phase II study, pts with untreated mPDA were randomized 1:1 to PAG (P; 3 µg/kg IV 2x/wk x wks C1, then 1x/wk C2+, plus AG) vs AG every 28 days. An imbalance thromboembolic (TE) events arm led a clinical hold (~40% discontinued PEGPH20),...
Background: Neurotrophic receptor tyrosine kinase (NTRK) gene fusions lead to the expression of chimeric TRK proteins with constitutively activated function, conferring oncogenic potential across several tumour types. Entrectinib is a CNS-active, potent inhibitor TRKA/B/C and ROS1. We present integrated efficacy safety data for entrectinib in NTRK fusion-positive (NTRK-FP) solid tumours focusing on pts NSCLC. Methods: Pts locally advanced/metastatic NTRK-FP (with or without baseline CNS...
439 Background: Poor outcome in pancreatic cancer (PDA) is associated partly with stromal hyaluronan (HA) accumulation, which compromises chemotherapy perfusion. PEGPH20, PEGylated recombinant human hyaluronidase, potentiates by depleting HA tumors. Methods: In an ongoing, phase II, open-label, randomized study of PEGPH20+nab-paclitaxel (Nab)+Gemcitabine (Gem) (PAG) vs Nab+Gem (AG) previously untreated stage IV PDA, pts receive PEGPH20 3 µg/kg twice weekly (C1), then (C2+) standard AG...