Pancreatic ductal adenocarcinoma: tumor microenvironment and problems in the development of novel therapeutic strategies

被引:14
作者
Kuznetsova, Alla [1 ,2 ]
Popova, Olga [1 ]
Panchenkov, Dmitry [1 ]
Dyuzheva, Tatyana [3 ]
Ivanov, Alexey [1 ]
机构
[1] AI Evdokimov Moscow State Univ Med & Dent, Minist Hlth Russian Federat, 20,Bld 1,Delegatskaya St, Moscow 127473, Russia
[2] Russian Acad Sci, Koltzov Inst Dev Biol, 26 Vavilov St, Moscow 119334, Russia
[3] IM Sechenov First Moscow State Med Univ, Sechenov Univ, Minist Hlth Russian Federat, 8-2 Trubetskaya St, Moscow 119991, Russia
关键词
Tumor microenvironment; Extracellular matrix; Cancer-associated fibroblasts; CAF heterogeneity; Pancreatic ductal adenocarcinoma; Stromal targeting; CARCINOMA-ASSOCIATED FIBROBLASTS; CANCER-ASSOCIATED FIBROBLASTS; PAPILLARY-MUCINOUS NEOPLASMS; FOCAL ADHESION KINASE; STELLATE CELLS; TGF-BETA; ANGIOTENSIN SYSTEM; GROWTH-FACTOR; SLIT-ROBO; RECEPTOR;
D O I
10.1007/s10238-022-00886-1
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Diagnosis and treatment of carcinoma of the exocrine part of the pancreas is a serious problem for modern medicine. Despite the identification of a large number of aberrant mutations in pancreatic ductal adenocarcinoma (PDAC), attempts to create effective therapeutic agents based on identified genetic or epigenetic variations have not been succesful. The role of the tumor microenvironment (TME) in tumor progression is currently a popular topic. Cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) are the main components of the tumor stroma and play an important role in the proliferation, invasiveness and metastasis of cancer. However, the mechanisms underlying the effect of CAFs and ECM on cancer progression are still unclear. Recent studies on stromal components and blockage of signaling pathways have brought some optimism to this area. New information on the role of TME will lead to the development of targeted therapies or combinations with modern chemotherapy for PDAC.
引用
收藏
页码:619 / 643
页数:25
相关论文
共 150 条
[91]   Tumor endothelial cells accelerate tumor metastasis [J].
Maishi, Nako ;
Hida, Kyoko .
CANCER SCIENCE, 2017, 108 (10) :1921-1926
[92]   Pancreatic cancer [J].
Maitra, Anirban ;
Hruban, Ralph H. .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2008, 3 :157-188
[93]   Tracking Down the Hedgehog's Lair in the Pancreas [J].
Maitra, Anirban .
GASTROENTEROLOGY, 2010, 138 (03) :823-825
[94]   Impact of the secretome of activated pancreatic stellate cells on growth and differentiation of pancreatic tumour cells [J].
Marzoq, Aseel J. ;
Mustafa, Shakhawan A. ;
Heidrich, Luzia ;
Hoheisel, Joerg D. ;
Alhamdani, Mohamed Saiel Saeed .
SCIENTIFIC REPORTS, 2019, 9 (1)
[95]   Differential roles of signaling pathways for proliferation and migration of rat pancreatic stellate cells [J].
Masamune, A ;
Kikuta, K ;
Satoh, M ;
Kume, K ;
Shimosegawa, T .
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 199 (02) :69-84
[96]   Ligands of peroxisome proliferator-activated receptor-γ block activation of pancreatic stellate cells [J].
Masamune, A ;
Kikuta, K ;
Satoh, M ;
Sakai, Y ;
Satoh, A ;
Shimosegawa, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (01) :141-147
[97]   The roles of tumor- and metastasis-promoting carcinoma-associated fibroblasts in human carcinomas [J].
Mezawa, Yoshihiro ;
Orimo, Akira .
CELL AND TISSUE RESEARCH, 2016, 365 (03) :675-689
[98]   Loss of the Transcription Factor GLI1 Identifies a Signaling Network in the Tumor Microenvironment Mediating KRAS Oncogene-induced Transformation [J].
Mills, Lisa D. ;
Zhang, Yaqing ;
Marler, Ronald J. ;
Herreros-Villanueva, Marta ;
Zhang, Lizhi ;
Almada, Luciana L. ;
Couch, Fergus ;
Wetmore, Cynthia ;
di Magliano, Marina Pasca ;
Fernandez-Zapico, Martin E. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (17) :11786-11794
[99]   Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer [J].
Misra, Suniti ;
Hascall, Vincent C. ;
Markwald, Roger R. ;
Ghatak, Shibnath .
FRONTIERS IN IMMUNOLOGY, 2015, 6
[100]   Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis [J].
Mizutani, Yasuyuki ;
Kobayashi, Hiroki ;
Iida, Tadashi ;
Asai, Naoya ;
Masamune, Atsushi ;
Hara, Akitoshi ;
Esaki, Nobutoshi ;
Ushida, Kaori ;
Mii, Shinji ;
Shiraki, Yukihiro ;
Ando, Kenju ;
Weng, Liang ;
Ishihara, Seiichiro ;
Ponik, Suzanne M. ;
Conklin, Matthew W. ;
Haga, Hisashi ;
Nagasaka, Arata ;
Miyata, Takaki ;
Matsuyama, Makoto ;
Kobayashi, Tomoe ;
Fujii, Tsutomu ;
Yamada, Suguru ;
Yamaguchi, Junpei ;
Wang, Tongtong ;
Woods, Susan L. ;
Worthley, Daniel ;
Shimamura, Teppei ;
Fujishiro, Mitsuhiro ;
Hirooka, Yoshiki ;
Enomoto, Atsushi ;
Takahashi, Masahide .
CANCER RESEARCH, 2019, 79 (20) :5367-5381