RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets

被引:3
作者
Chen, Shao-Long [1 ]
Wang, Guo-Ping [2 ]
Shi, Dan-Rong [3 ]
Yao, Shu-Hao [4 ]
Chen, Ke-Da [1 ]
Yao, Hang-Ping [3 ]
机构
[1] Zhejiang Shuren Univ, Shulan Int Med Coll, Hangzhou 310000, Zhejiang, Peoples R China
[2] Zhejiang Chinese Med Univ, Affiliated Hosp 2, Dept Surg Oncol, Hangzhou 310000, Zhejiang, Peoples R China
[3] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Natl Clin Res Ctr Infect Dis,State Key Lab Diag &, 79 Qingchun Rd, Hangzhou 310000, Zhejiang, Peoples R China
[4] Wenzhou Med Univ, Dept Stomatol, Renji Coll, Wenzhou 325035, Zhejiang, Peoples R China
关键词
RON; Signal transduction; Hepatobiliary; Pancreatic neoplasms; Molecular targeted therapy; RECEPTOR TYROSINE KINASE; MACROPHAGE-STIMULATING PROTEIN; SMALL-MOLECULE INHIBITOR; C-MET; PROGNOSTIC-SIGNIFICANCE; MESENCHYMAL TRANSITION; ONCOGENIC PHENOTYPES; ALTERED EXPRESSION; TUMOR PROGRESSION; GENE-PRODUCT;
D O I
10.3748/wjg.v27.i20.2507
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family. Research has shown that RON has a role in cancer pathogenesis, which places RON on the frontline of the development of novel cancer therapeutic strategies. Hepatobiliary and pancreatic (HBP) cancers have a poor prognosis, being reported as having higher rates of cancer-related death. Therefore, to combat these malignant diseases, the mechanism underlying the aberrant expression and signaling of RON in HBP cancer pathogenesis, and the development of RON as a drug target for therapeutic intervention should be investigated. Abnormal RON expression and signaling have been identified in HBP cancers, and also act as tumorigenic determinants for HBP cancer malignant behaviors. In addition, RON is emerging as an important mediator of the clinical prognosis of HBP cancers. Thus, not only is RON significant in HBP cancers, but also RON-targeted therapeutics could be developed to treat these cancers, for example, therapeutic monoclonal antibodies and small-molecule inhibitors. Among them, antibody-drug conjugates have become increasingly popular in current research and their potential as novel anti-cancer biotherapeutics will be determined in future clinical trials.
引用
收藏
页码:2507 / 2520
页数:14
相关论文
共 93 条
[1]   MST1R kinase accelerates pancreatic cancer progression via effects on both epithelial cells and macrophages [J].
Babicky, Michele L. ;
Harper, Megan M. ;
Chakedis, Jeffery ;
Cazes, Alex ;
Mose, Evangeline S. ;
Jaquish, Dawn, V ;
French, Randall P. ;
Childers, Betzaira ;
Alakus, Hakan ;
Schmid, Michael C. ;
Foubert, Phillippe ;
Miyamoto, Jaclyn ;
Holman, Patrick J. ;
Walterscheid, Zakkary J. ;
Tang, Chih-Min ;
Varki, Nissi ;
Sicklick, Jason K. ;
Messer, Karen ;
Varner, Judith A. ;
Waltz, Susan E. ;
Lowy, Andrew M. .
ONCOGENE, 2019, 38 (28) :5599-5611
[2]   Truncated RON tyrosine kinase drives tumor cell progression and abrogates cell-cell adhesion through E-cadherin transcriptional repression [J].
Bardella, C ;
Costa, B ;
Maggiora, P ;
Patane, S ;
Olivero, M ;
Ranzani, GN ;
De Bortoli, M ;
Comoglio, PM ;
Di Renzo, MF .
CANCER RESEARCH, 2004, 64 (15) :5154-5161
[3]   Identification and developmental expression of a macrophage stimulating 1/hepatocyte growth factor-like 1 orthologue in the zebrafish [J].
Bassett, DI .
DEVELOPMENT GENES AND EVOLUTION, 2003, 213 (07) :360-362
[4]  
Belalcazar A, 2012, EXPERT REV ANTICANC, V12, P519, DOI [10.1586/era.12.16, 10.1586/ERA.12.16]
[5]   Role of MED1 (MBD4) gene in DNA repair and human cancer [J].
Bellacosa, A .
JOURNAL OF CELLULAR PHYSIOLOGY, 2001, 187 (02) :137-144
[6]   Ron receptor tyrosine kinase signaling as a therapeutic target [J].
Benight, Nancy M. ;
Waltz, Susan E. .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2012, 16 (09) :921-931
[7]   Tyrosine kinase receptor RON in human pancreatic cancer - Expression, function, and validation as a target [J].
Camp, E. Ramsay ;
Yang, Anthony ;
Gray, Mike J. ;
Fan, Fan ;
Hamilton, Stanley R. ;
Evans, Douglas B. ;
Hooper, Andrea T. ;
Pereira, Daniel S. ;
Hicklin, Daniel J. ;
Ellis, Lee M. .
CANCER, 2007, 109 (06) :1030-1039
[8]   RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma [J].
Catenacci, Daniel V. T. ;
Cervantes, Gustavo ;
Yala, Soheil ;
Nelson, Erik A. ;
El-Hashani, Essam ;
Kanteti, Rajani ;
El Dinali, Mohamed ;
Hasina, Rifat ;
Braegelmann, Johannes ;
Seiwert, Tanguy ;
Sanicola, Michele ;
Henderson, Les ;
Grushko, Tatyana A. ;
Olopade, Olufunmilayo ;
Karrison, Theodore ;
Bang, Yung-Jue ;
Kim, Woo Ho ;
Tretiakova, Maria ;
Vokes, Everett ;
Frank, David A. ;
Kindler, Hedy L. ;
Huet, Heather ;
Salgia, Ravi .
CANCER BIOLOGY & THERAPY, 2011, 12 (01) :9-46
[9]   Roles of c-Met and RON Kinases in tumor progression and their potential as therapeutic targets [J].
Chang, Katherine ;
Karnad, Anand ;
Zhao, Shujie ;
Freeman, James W. .
ONCOTARGET, 2015, 6 (06) :3507-3518
[10]  
Chen QY, 1997, HEPATOLOGY, V26, P59