A5008330168- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Immune cells in cancer
- Colorectal Cancer Treatments and Studies
- Neuroendocrine Tumor Research Advances
- Immunotherapy and Immune Responses
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- PI3K/AKT/mTOR signaling in cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Treatment and Pharmacology
- Melanoma and MAPK Pathways
- Cancer therapeutics and mechanisms
- Pancreatitis Pathology and Treatment
- Renal cell carcinoma treatment
- CAR-T cell therapy research
- Gastric Cancer Management and Outcomes
- Cancer Mechanisms and Therapy
- Neuroblastoma Research and Treatments
- Chemokine receptors and signaling
- Glioma Diagnosis and Treatment
Washington University in St. Louis
2016-2025
Jewish Hospital
2014-2024
Barnes-Jewish Hospital
2014-2024
University Hospitals Seidman Cancer Center
2024
Weatherford College
2023
Medical University of South Carolina
2021
Dartmouth–Hitchcock Medical Center
2021
Molecular Oncology (United States)
2020
German Cancer Research Center
2019
Heidelberg University
2019
Abstract Cancer immunotherapy generally offers limited clinical benefit without coordinated strategies to mitigate the immunosuppressive nature of tumor microenvironment. Critical drivers immune escape in microenvironment include tumor-associated macrophages and myeloid-derived suppressor cells, which not only mediate suppression, but also promote metastatic dissemination impart resistance cytotoxic therapies. Thus, ablate effects these myeloid cell populations may offer great therapeutic...
Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors. Consequently, the type quality of responses present neoplastic stroma are highly predictive patient outcome several cancer types. In addition to host responses, intrinsic tumor cell activities that mimic stem properties have been linked chemoresistance, dissemination, induction suppression. Cancer far from a static population; rather, their presence seems be controlled by dynamic processes...
To determine the role of CCL2/CCR2 axis and inflammatory monocytes (CCR2(+)/CD14(+)) as immunotherapeutic targets in treatment pancreatic cancer.Survival analysis was conducted to if prevalence preoperative blood correlates with survival patients cancer following tumor resection. Inflammatory monocyte bone marrow controls compared. The immunosuppressive properties macrophages tumors, respectively, were assessed. CCL2 expression by human tumors compared normal pancreas. A novel CCR2 inhibitor...
Purpose GVAX pancreas, granulocyte-macrophage colony-stimulating factor–secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. is administered with low-dose cyclophosphamide (Cy) inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes–expressing mesothelin, innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination CRS-207 in adenocarcinoma. Patients Methods Previously...
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...
Ulixertinib (BVD-523) is an ERK1/2 kinase inhibitor with potent preclinical activity in BRAF- and RAS-mutant cell lines. In this multicenter phase I trial (NCT01781429), 135 patients were enrolled to accelerated 3 + dose-escalation cohort six distinct dose-expansion cohorts. Dose escalation included 27 patients, dosed from 10 900 mg twice daily established the recommended II dose (RP2D) of 600 daily. exposure was proportional RP2D, which provided near-complete inhibition ERK whole blood....
Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report final analysis baseline characteristics associated long-term survivors (survival of ≥1 year)...
Clinical outcomes after curative treatment of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. To assess the potential early control systemic disease with multiagent perioperative chemotherapy, we conducted a prospective trial.
Pancreatic cancer (PC) mobilizes myeloid cells from the bone marrow to tumor where they promote growth and proliferation. Cancer stem (CSCs) are a population of that responsible for initiation. Aldehyde dehydrogenase-1 activity in PC identifies CSCs, its has been correlated with poor overall prognosis human PC. Myeloid have shown impact stemness, but immunosuppressive tumor-infiltrating granulocytic monocytic myeloid-derived suppressor (Mo-MDSC) on ALDH1(Bright) CSCs epithelial mesenchymal...
Objective: The optimal neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDA) and the impact on surgical outcomes remains unclear. Methods: S1505 (NCT02562716) was a randomized phase II study of perioperative chemotherapy with mFOLFIRINOX (Arm 1) or gemcitabine/nab-paclitaxel 2). Measured parameters included resection rate, margin positivity, pathologic response, toxicity. Results: Between 2015 2018, 147 patients were randomized. Of these, 44 (30%) deemed ineligible (43 by...
How the
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.
Targeting the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) holds promise to augment effect chemotherapy, but success in clinic has thus far been limited. Preclinical mouse models suggest that near-depletion cancer-associated fibroblasts (CAF) carries a risk accelerating PDAC progression, underscoring need concurrently target key signaling mechanisms drive malignant attributes both CAF and cells. We previously reported inhibition IL1 receptor-associated kinase 4 (IRAK4)...
Tumor–stroma interactions contribute to tumorigenesis. Tumor cells can educate the stroma at primary and distant sites facilitate recruitment of heterogeneous populations immature myeloid cells, known as myeloid-derived suppressor (MDSCs). MDSCs suppress T cell responses promote tumor proliferation. One outstanding question is how local modulate during progression. Down-regulation β-catenin critical for MDSC accumulation immune suppressive functions in mice humans. Here, we demonstrate that...