A5037755647- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Hepatocellular Carcinoma Treatment and Prognosis
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Angiogenesis and VEGF in Cancer
- Neuroendocrine Tumor Research Advances
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Proteoglycans and glycosaminoglycans research
- Cancer Treatment and Pharmacology
- PI3K/AKT/mTOR signaling in cancer
- Cancer Research and Treatments
- Lung Cancer Research Studies
- Chronic Lymphocytic Leukemia Research
- Genetic factors in colorectal cancer
- Multiple and Secondary Primary Cancers
- Lung Cancer Treatments and Mutations
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Colorectal Cancer Surgical Treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immune Cell Function and Interaction
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
Hoag Memorial Hospital Presbyterian
2022-2024
University of California, Irvine
2012-2019
University of California, Irvine Medical Center
2011-2019
Fred Hutch Cancer Center
2017
Beth Israel Deaconess Medical Center
2017
Johns Hopkins University
2017
Cancer Research Center
2017
UC Irvine Health
2016
Palmetto Hematology Oncology
2015
University of Illinois Chicago
2009
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...
Pegylated recombinant human hyaluronidase (PEGPH20) degrades hyaluronan (HA) and, in combination with chemotherapy, prolongs survival preclinical models. The activity of PEGPH20 modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) was evaluated patients metastatic pancreatic cancer (mPC).
KRAS mutations are common in pancreatic cancer, but directly targeting the protein has thus far been unsuccessful. The aim of this trial was to block MEK and PI3K/AKT pathways downstream as an alternate treatment strategy slow cancer growth prolong survival. This first cooperative group evaluate using molecularly targeted oral combination therapy for chemotherapy-refractory cancer.
Abstract RET fusions are oncogenic drivers of various tumors, including non–small cell lung cancers (NSCLC). The safety and antitumor activity the multikinase inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended II dose 275 mg fed daily was identified. most common treatment-related adverse events fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash nonmaculopapular (17%). In Ib cohort inhibitor–naïve patients with fusion–positive NSCLCs, objective...
There is an unmet clinical need for molecularly directed therapies available metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable alterations in Through comprehensive we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, cancer (CRC) patients. kinases represent a class oncogenic driver CRC occurred at 0.2% frequency without concurrent mutations, KRAS, NRAS, BRAF, PIK3CA or other tyrosine...
BACKGROUND The AKT inhibitor MK‐2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers. METHODS Patients who had progressed after first‐line treatment were eligible. Pertinent eligibility criteria included adequate organ function, fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. given orally (60 evaluable patients required). primary endpoint overall survival, median survival 6.5 months (power, 89%;...
Background: Precision medicine relies on mutational profiling, but clinical actionability remains limited for many cancer patients. We evaluated the feasibility and of ex-vivo drug sensitivity testing across solid tumors, focusing rare cancers. This study uses PARIS® CLIA-certified test, assessing patient-derived tumor cells (PDTCs) responses to a broad oncology panel. Methods: Tumor specimens (biopsies, fluids, or surgical samples) were shipped our laboratory arrive within 48h cultured in...
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 Metastatic pancreatic cancer (mPC) is an aggressive form of with a poor prognosis and few therapeutic options after failure the second-line treatment. Induction immunogenic cell death (ICD) by use relatively low-dose chemo- or radiation therapy, enhancement immune responses IL-15 superagonist N-803 (Anktiva ® ), targeting programmed receptor ligand 1 (PD-L1)-expressing cells may offer approach to refractory mPC potential increase overall survival (OS). Methods From late 2019 2021,...
208 Background: PEGPH20 degrades hyaluronan (HA), a major component of the stroma, increases delivery gemcitabine and prolongs survival in preclinical models. We evaluated activity combination with mFFOX mPC , unselected for tumor HA. Methods: Pertinent eligibility: untreated mPC, PS 0-1 adequate organ function. Standard FFOX was modified to add prophylactic growth factor support omit bolus 5FU. Due increased thromboembolic (TE) events PEGPH20, an amendment instituted LMWH prophylaxis arm...
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...
720 Background: Pancreatic cancer claimed an estimated 47,050 lives in the USA 2020, with expected median overall survival (OS) of 3 months 3rd line. (Manax ASCO GI 2019), no evidence disease control these late stage patients. We hypothesize that effective response against pancreatic requires orchestration both innate and adaptive immune system to accomplish immunogenic cell death benefit. Herein we report updated results fully enrolled cohort a novel combination immunotherapy protocol...
TPS4210 Background: VCN-01 is a modified oncolytic adenovirus type 5 (Ad5) designed to replicate selectively in cancer cells with dysfunctional RB1-E2F pathway and express hyaluronidase enhance virus intratumoral spread facilitate chemotherapy immune extravasation into the tumor. Results obtained previous phase I trial patients solid tumors, including metastatic pancreatic cancer, showed that single systemic administration of feasible has an acceptable safety profile alone or when combined...
12117 Background: Next generation sequencing (NGS) Gene panel testing is used to imputed tumor mutational burden (iTMB) and has shown rough correlation with TMB derived from whole exome (WES). estimate immune checkpoint inhibitor (ICT) response based on potential neoantigen load. We hypothesized that actual (aTMB), consisting of mutations across the exome, expressed (eTMB), genes, would differ substantially iTMB. Methods: Retrospective analysis a database commercial DNA tumor:normal RNAseq...
TPS463 Background: Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead the creation of an suppressive tumor microenvironment. We hypothesize effective and sustained response against tumors requires a coordinated approach that: 1. reverses immune-suppressive microenvironment, 2. induces immunogenic cell death 3. reengages NK T-cell 4. cascade antigens. To test this hypothesis, we developed NANT Cancer Vaccine (NCV), which combines metronomic low-dose...
Abstract TNBC is an aggressive subtype of breast cancer with limited treatment options. We hypothesize that effective response against requires a coordinated approach orchestrates both the innate and adaptive immune system. further by orchestrating activation entire system, we could accomplish immunogenic cell death durable responses in this disease. describe first-in-human novel combination immunotherapy protocol chemoradiation, cytokine-induced NK T activation, checkpoint inhibition,...
582 Background: Pancreatic cancer claimed an estimated 47,050 lives in the USA 2020, with expected median overall survival (OS) of 3 months 3rd line. (Manax ASCO GI 2019), no evidence disease control these late stage patients. We hypothesize that effective response against pancreatic requires orchestration both innate and adaptive immune system to accomplish immunogenic cell death benefit. Herein we report first results a novel combination immunotherapy protocol low-dose chemoradiation,...
Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability differentiate histologically into two distinct tumor types. hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although rare tumor, is important for clinicians recognize, since treatment options targeting both elements of the are crucial. Imaging findings bi-phenotypic HCC-CC not specific and include features HCC CC. A combination imaging immuno-histochemical analysis usually needed make...