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Pancreatic Neoplasms: HELP
Articles by Deirdre J. Cohen
Based on 5 articles published since 2009
(Why 5 articles?)

Between 2009 and 2019, D. J. Cohen wrote the following 5 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Clinical Trial Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer. 2015

Catenacci, Daniel V T / Junttila, Melissa R / Karrison, Theodore / Bahary, Nathan / Horiba, Margit N / Nattam, Sreenivasa R / Marsh, Robert / Wallace, James / Kozloff, Mark / Rajdev, Lakshmi / Cohen, Deirdre / Wade, James / Sleckman, Bethany / Lenz, Heinz-Josef / Stiff, Patrick / Kumar, Pankaj / Xu, Peng / Henderson, Les / Takebe, Naoko / Salgia, Ravi / Wang, Xi / Stadler, Walter M / de Sauvage, Frederic J / Kindler, Hedy L. ·Daniel V.T. Catenacci, Theodore Karrison, James Wallace, Mark Kozloff, Peng Xu, Les Henderson, Ravi Salgia, Walter M. Stadler, Hedy L. Kindler, University of Chicago Medical Center · Patrick Stiff, Loyola University Medical Center, Chicago · Robert Marsh, Northshore University Health System, Evanston · James Wallace, Mark Kozloff, Ingalls Hospital, Harvey · James Wade, Decatur Memorial Hospital, Decatur · Pankaj Kumar, Oncology/Hematology Associates, Peoria, IL · Melissa R. Junttila, Xi Wang, and Frederic J. de Sauvage, Genentech, South San Francisco · Heinz-Josef Lenz, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA · Nathan Bahary, University of Pittsburgh Cancer Institute, Pittsburgh, PA · Margit N. Horiba, University of Maryland Greenebaum Cancer Center, Baltimore, MD · Sreenivasa R. Nattam, Ft Wayne Medical Oncology/Hematology, Ft Wayne, IN · Lakshmi Rajdev, Montefiore Medical Center, Bronx · Deirdre Cohen, New York University Cancer Center, New York, NY · Bethany Sleckman, St John's Mercy Medical Center, St Louis, MO · and Naoko Takebe, National Cancer Institute, National Institutes of Health, Bethesda, MD. ·J Clin Oncol · Pubmed #26527777.

ABSTRACT: PURPOSE: Sonic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in > 70% of pancreatic cancers (PCs). We investigated the impact of vismodegib, an SHH antagonist, plus gemcitabine (GV) or gemcitabine plus placebo (GP) in a multicenter phase Ib/randomized phase II trial and preclinical PC models. PATIENTS AND METHODS: Patients with PC not amenable to curative therapy who had received no prior therapy for metastatic disease and had Karnofsky performance score ≥ 80 were enrolled. Patients were randomly assigned in a one-to-one ratio to GV or GP. The primary end point was progression-free-survival (PFS). Exploratory correlative studies included serial SHH serum levels and contrast perfusion computed tomography imaging. To further investigate putative biologic mechanisms of SMO inhibition, two autochthonous pancreatic cancer models (Kras(G12D); p16/p19(fl/fl); Pdx1-Cre and Kras(G12D); p53(R270H/wt); Pdx1-Cre) were studied. RESULTS: No safety issues were identified in the phase Ib portion (n = 7), and the phase II study enrolled 106 evaluable patients (n = 53 in each arm). Median PFS was 4.0 and 2.5 months for GV and GP arms, respectively (95% CI, 2.5 to 5.3 and 1.9 to 3.8, respectively; adjusted hazard ratio, 0.81; 95% CI, 0.54 to 1.21; P = .30). Median overall survival (OS) was 6.9 and 6.1 months for GV and GP arms, respectively (95% CI, 5.8 to 8.0 and 5.0 to 8.0, respectively; adjusted hazard ratio, 1.04; 95% CI, 0.69 to 1.58; P = .84). Response rates were not significantly different. There were no significant associations between correlative markers and overall response rate, PFS, or OS. Preclinical trials revealed no significant differences with vismodegib in drug delivery, tumor growth rate, or OS in either model. CONCLUSION: The addition of vismodegib to gemcitabine in an unselected cohort did not improve overall response rate, PFS, or OS in patients with metastatic PC. Our preclinical and clinical results revealed no statistically significant differences with respect to drug delivery or treatment efficacy using vismodegib.

2 Clinical Trial A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. 2015

O'Neil, B H / Scott, A J / Ma, W W / Cohen, S J / Leichman, L / Aisner, D L / Menter, A R / Tejani, M A / Cho, J K / Granfortuna, J / Coveler, A L / Olowokure, O O / Baranda, J C / Cusnir, M / Phillip, P / Boles, J / Nazemzadeh, R / Rarick, M / Cohen, D J / Radford, J / Fehrenbacher, L / Bajaj, R / Bathini, V / Fanta, P / Berlin, J / McRee, A J / Maguire, R / Wilhelm, F / Maniar, M / Jimeno, A / Gomes, C L / Messersmith, W A. ·Simon Cancer Center, Indiana University School of Medicine, Indianapolis. · University of Colorado, Denver, Aurora. · Roswell Park Cancer Institute, Buffalo. · Fox Chase Cancer Center, Philadelphia. · Kaiser Permanente, Lone Tree. · University of Rochester Medical Center, Rochester. · Oncare Hawaii, Honolulu. · Cone Health Cancer Center, Greensboro. · University of Washington, Seattle. · University of Cincinnati Cancer Institute, Cincinnati. · University of Kansas Medical Center, Westwood. · Mount Sinai Medical Center, Miami Beach. · Karmanos Cancer Institute, Detroit. · Rex Cancer Center UNC Healthcare, Raleigh. · Carolinas Health Care, Charlotte. · Kaiser Permanante Northwest, Portland. · NYU Clinical Cancer Center, New York. · Hendersonville Hematology and Oncology at Pardee, Hendersonville. · Kaiser Permanante Medical Center, Vallejo. · McLeod Regional Medical Center, Florence. · University of Massachusetts Memorial, Worcester. · UCSD Moores Cancer Center, La Jolla. · Vanderbilt-Ingram Cancer Center, Nashville. · UNC Lineberger Comprehensive Cancer Center, Chapel Hill. · Onconova Therapeutics Inc., Newtown. · Oncology Consortia of Criterium Inc., Saratoga Springs, USA. · University of Colorado, Denver, Aurora wells.messersmith@ucdenver.edu. ·Ann Oncol · Pubmed #26091808.

ABSTRACT: BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.

3 Clinical Trial Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. 2015

Le, Dung T / Wang-Gillam, Andrea / Picozzi, Vincent / Greten, Tim F / Crocenzi, Todd / Springett, Gregory / Morse, Michael / Zeh, Herbert / Cohen, Deirdre / Fine, Robert L / Onners, Beth / Uram, Jennifer N / Laheru, Daniel A / Lutz, Eric R / Solt, Sara / Murphy, Aimee Luck / Skoble, Justin / Lemmens, Ed / Grous, John / Dubensky, Thomas / Brockstedt, Dirk G / Jaffee, Elizabeth M. ·Dung T. Le, Beth Onners, Jennifer N. Uram, Daniel A. Laheru, Eric R. Lutz, Sara Solt, and Elizabeth M. Jaffee, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore · Tim F. Greten, National Cancer Institute, Bethesda, MD · Andrea Wang-Gillam, Siteman Cancer Center, Washington University, St Louis, MO · Vincent Picozzi, Virginia Mason Medical Center, Seattle, WA · Todd Crocenzi, Providence Portland Medical Center, Portland, OR · Gregory Springett, Moffitt Cancer Center, Tampa, FL · Michael Morse, Duke University Medical Center, Durham, NC · Herbert Zeh, University of Pittsburgh, Pittsburgh, PA · Deirdre Cohen, New York University Langone Medical Center · Robert L. Fine, Columbia University Medical Center, New York, NY · and Aimee Luck Murphy, Justin Skoble, Ed Lemmens, John Grous, Thomas Dubensky Jr, and Dirk G. Brockstedt, Aduro BioTech, Berkeley, CA. ·J Clin Oncol · Pubmed #25584002.

ABSTRACT: PURPOSE: GVAX pancreas, granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer antigens, including mesothelin. GVAX is administered with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated Listeria monocytogenes-expressing mesothelin, induces innate and adaptive immunity. On the basis of preclinical synergy, we tested prime/boost vaccination with GVAX and CRS-207 in pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously treated patients with metastatic pancreatic adenocarcinoma were randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable patients were offered additional courses. The primary end point was overall survival (OS) between arms. Secondary end points were safety and clinical response. RESULTS: A total of 90 patients were treated (arm A, n = 61; arm B, n = 29); 97% had received prior chemotherapy; 51% had received ≥ two regimens for metastatic disease. Mean number of doses (± standard deviation) administered in arms A and B were 5.5 ± 4.5 and 3.7 ± 2.2, respectively. The most frequent grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of patients who received at least three doses (two doses of Cy/GVAX plus one of CRS-207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P = .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with longer OS, regardless of treatment arm. CONCLUSION: Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity.

4 Article RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer. 2018

Wang, Wei / Marinis, Jill M / Beal, Allison M / Savadkar, Shivraj / Wu, Yue / Khan, Mohammed / Taunk, Pardeep S / Wu, Nan / Su, Wenyu / Wu, Jingjing / Ahsan, Aarif / Kurz, Emma / Chen, Ting / Yaboh, Inedouye / Li, Fei / Gutierrez, Johana / Diskin, Brian / Hundeyin, Mautin / Reilly, Michael / Lich, John D / Harris, Philip A / Mahajan, Mukesh K / Thorpe, James H / Nassau, Pamela / Mosley, Julie E / Leinwand, Joshua / Kochen Rossi, Juan A / Mishra, Ankita / Aykut, Berk / Glacken, Michael / Ochi, Atsuo / Verma, Narendra / Kim, Jacqueline I / Vasudevaraja, Varshini / Adeegbe, Dennis / Almonte, Christina / Bagdatlioglu, Ece / Cohen, Deirdre J / Wong, Kwok-Kin / Bertin, John / Miller, George. ·S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 435 East 30th Street, 4th Floor, New York, NY 10016, USA. · Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. · Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. · Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. · Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. Electronic address: john.j.bertin@gsk.com. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 435 East 30th Street, 4th Floor, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. Electronic address: george.miller@nyumc.org. ·Cancer Cell · Pubmed #30423296.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 (RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCII

5 Article The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. 2018

Pushalkar, Smruti / Hundeyin, Mautin / Daley, Donnele / Zambirinis, Constantinos P / Kurz, Emma / Mishra, Ankita / Mohan, Navyatha / Aykut, Berk / Usyk, Mykhaylo / Torres, Luisana E / Werba, Gregor / Zhang, Kevin / Guo, Yuqi / Li, Qianhao / Akkad, Neha / Lall, Sarah / Wadowski, Benjamin / Gutierrez, Johana / Kochen Rossi, Juan Andres / Herzog, Jeremy W / Diskin, Brian / Torres-Hernandez, Alejandro / Leinwand, Josh / Wang, Wei / Taunk, Pardeep S / Savadkar, Shivraj / Janal, Malvin / Saxena, Anjana / Li, Xin / Cohen, Deirdre / Sartor, R Balfour / Saxena, Deepak / Miller, George. ·Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York. · National Gnotobiotic Rodent Research Center, University of North Carolina, Chapel Hill, North Carolina. · Department of Epidemiology and Health Promotion, NYU College of Dentistry, New York, New York. · Department of Biology, Brooklyn College and the Graduate Center (CUNY), Brooklyn, New York, New York. · Department of Medicine, New York University School of Medicine, New York, New York. · Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York. george.miller@nyumc.org ds100@nyu.edu. · S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York. george.miller@nyumc.org ds100@nyu.edu. · Department of Medicine, Microbiology, and Immunology, University of North Carolina, Chapel Hill, North Carolina. ·Cancer Discov · Pubmed #29567829.

ABSTRACT: We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4