Improving theranostics in pancreatic cancer

被引:21
作者
King, Jeremy [1 ]
Bouvet, Michael [2 ]
Singh, Gagandeep [3 ]
Williams, John [1 ]
机构
[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Med, 1710 Flower St, Duarte, CA 91010 USA
[2] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA
[3] City Hope Natl Med Ctr, Dept Surg, 1500 Flower St, Duarte, CA 91010 USA
关键词
antibody engineering; site directed conjugation; theranostics; LIVER RECEPTOR HOMOLOG-1; STRUCTURAL BASIS; BETA-CATENIN; LRH-1; PROLIFERATION; NR5A2;
D O I
10.1002/jso.24625
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Pancreatic cancer is the fourth most deadly cancer in the United States, and is expected to be the second most deadly by 2030. The major difficulty in treating pancreatic cancer is the late onset of symptoms. Generally, patients show metastatic disease by the time of diagnosis, with a survival rate of 5% beyond 5 years. In patients without metastatic disease, surgical resection increases 5 year survival rate to 25%. The remaining 75% succumb to undetected metastases. Clearly, improvements to both detection, surgical intervention, and therapeutic strategies will be needed to improve patient outcome in pancreatic cancer. Methods: Recent literature has been surveyed and atomic models of new therapeutic approaches were generated. Results and Conclusions: Here, we focus on the recent progress employing monoclonal antibodies (mAbs) to target pancreatic cancer associated markers, and more specifically on recent chemical and protein engineering efforts to improve the homogeneity, stability, and administration of mAbs to precisely deliver imaging agents and cytotoxins to sites of disease.
引用
收藏
页码:104 / 113
页数:10
相关论文
共 12 条
[1]   Structure-based Discovery of Antagonists of Nuclear Receptor LRH-1 [J].
Benod, Cindy ;
Carlsson, Jens ;
Uthayaruban, Rubatharshini ;
Hwang, Peter ;
Irwin, John J. ;
Doak, Allison K. ;
Shoichet, Brian K. ;
Sablin, Elena P. ;
Fletterick, Robert J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (27) :19830-19844
[2]   Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation [J].
Benod, Cindy ;
Vinogradova, Maia V. ;
Jouravel, Natalia ;
Kim, Grace E. ;
Fletterick, Robert J. ;
Sablin, Elena P. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (41) :16927-16931
[3]   Synergy between LRH-1 and β-catenin induces G1 cyclin-mediated cell proliferation [J].
Botrugno, OA ;
Fayard, E ;
Annicotte, JS ;
Haby, C ;
Brennan, T ;
Wendling, O ;
Tanaka, T ;
Kodama, T ;
Thomas, W ;
Auwerx, J ;
Schoonjans, K .
MOLECULAR CELL, 2004, 15 (04) :499-509
[4]   Disulfide-Trapping Identifies a New, Effective Chemical Probe for Activating the Nuclear Receptor Human LRH-1 (NR5A2) [J].
Cortez, Felipe de Jesus ;
Suzawa, Miyuki ;
Irvy, Sam ;
Bruning, John M. ;
Sablin, Elena ;
Jacobson, Matthew P. ;
Fletterick, Robert J. ;
Ingraham, Holly A. ;
England, Pamela M. .
PLOS ONE, 2016, 11 (07)
[5]   A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33 [J].
Petersen, Gloria M. ;
Amundadottir, Laufey ;
Fuchs, Charles S. ;
Kraft, Peter ;
Stolzenberg-Solomon, Rachael Z. ;
Jacobs, Kevin B. ;
Arslan, Alan A. ;
Bueno-de-Mesquita, H. Bas ;
Gallinger, Steven ;
Gross, Myron ;
Helzlsouer, Kathy ;
Holly, Elizabeth A. ;
Jacobs, Eric J. ;
Klein, Alison P. ;
LaCroix, Andrea ;
Li, Donghui ;
Mandelson, Margaret T. ;
Olson, Sara H. ;
Risch, Harvey A. ;
Zheng, Wei ;
Albanes, Demetrius ;
Bamlet, William R. ;
Berg, Christine D. ;
Boutron-Ruault, Marie-Christine ;
Buring, Julie E. ;
Bracci, Paige M. ;
Canzian, Federico ;
Clipp, Sandra ;
Cotterchio, Michelle ;
de Andrade, Mariza ;
Duell, Eric J. ;
Gaziano, J. Michael ;
Giovannucci, Edward L. ;
Goggins, Michael ;
Hallmans, Goran ;
Hankinson, Susan E. ;
Hassan, Manal ;
Howard, Barbara ;
Hunter, David J. ;
Hutchinson, Amy ;
Jenab, Mazda ;
Kaaks, Rudolf ;
Kooperberg, Charles ;
Krogh, Vittorio ;
Kurtz, Robert C. ;
Lynch, Shannon M. ;
McWilliams, Robert R. ;
Mendelsohn, Julie B. ;
Michaud, Dominique S. ;
Parikh, Hemang .
NATURE GENETICS, 2010, 42 (03) :224-U29
[6]   Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket [J].
Sablin, Elena P. ;
Blind, Raymond D. ;
Uthayaruban, Rubatharshini ;
Chiu, Hsiu-Ju ;
Deacon, Ashley M. ;
Das, Debanu ;
Ingraham, Holly A. ;
Fletterick, Robert J. .
JOURNAL OF STRUCTURAL BIOLOGY, 2015, 192 (03) :342-348
[7]   Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1 [J].
Sablin, EP ;
Krylova, IN ;
Fletterick, RJ ;
Ingraham, HA .
MOLECULAR CELL, 2003, 11 (06) :1575-1585
[8]   Molecular basis for the regulation of the nuclear receptor LRH-1 [J].
Stein, Sokrates ;
Schoonjans, Kristina .
CURRENT OPINION IN CELL BIOLOGY, 2015, 33 :26-34
[9]   Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation [J].
von Figura, Guido ;
Morris, John P. ;
Wright, Christopher V. E. ;
Hebrok, Matthias .
GUT, 2014, 63 (04) :656-664
[10]   Canonical Wnt/β-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression [J].
Wagner, Ryan T. ;
Xu, Xueping ;
Yi, Fei ;
Merrill, Bradley J. ;
Cooney, Austin J. .
STEM CELLS, 2010, 28 (10) :1794-1804