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
[21]   Single-Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression [J].
Bernard, Vincent ;
Semaan, Alexander ;
Huang, Jonathan ;
San Lucas, F. Anthony ;
Mulu, Feven C. ;
Stephens, Bret M. ;
Guerrero, Paola A. ;
Huang, Yanqing ;
Zhao, Jun ;
Kamyabi, Nabiollah ;
Sen, Subrata ;
Scheet, Paul A. ;
Taniguchi, Cullen M. ;
Kim, Michael P. ;
Tzeng, Ching-Wei ;
Katz, Matthew H. ;
Singhi, Aatur D. ;
Maitra, Anirban ;
Alvarez, Hector A. .
CLINICAL CANCER RESEARCH, 2019, 25 (07) :2194-2205
[22]   Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes [J].
Biankin, Andrew V. ;
Waddell, Nicola ;
Kassahn, Karin S. ;
Gingras, Marie-Claude ;
Muthuswamy, Lakshmi B. ;
Johns, Amber L. ;
Miller, David K. ;
Wilson, Peter J. ;
Patch, Ann-Marie ;
Wu, Jianmin ;
Chang, David K. ;
Cowley, Mark J. ;
Gardiner, Brooke B. ;
Song, Sarah ;
Harliwong, Ivon ;
Idrisoglu, Senel ;
Nourse, Craig ;
Nourbakhsh, Ehsan ;
Manning, Suzanne ;
Wani, Shivangi ;
Gongora, Milena ;
Pajic, Marina ;
Scarlett, Christopher J. ;
Gill, Anthony J. ;
Pinho, Andreia V. ;
Rooman, Ilse ;
Anderson, Matthew ;
Holmes, Oliver ;
Leonard, Conrad ;
Taylor, Darrin ;
Wood, Scott ;
Xu, Qinying ;
Nones, Katia ;
Fink, J. Lynn ;
Christ, Angelika ;
Bruxner, Tim ;
Cloonan, Nicole ;
Kolle, Gabriel ;
Newell, Felicity ;
Pinese, Mark ;
Mead, R. Scott ;
Humphris, Jeremy L. ;
Kaplan, Warren ;
Jones, Marc D. ;
Colvin, Emily K. ;
Nagrial, Adnan M. ;
Humphrey, Emily S. ;
Chou, Angela ;
Chin, Venessa T. ;
Chantrill, Lorraine A. .
NATURE, 2012, 491 (7424) :399-405
[23]   IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma [J].
Biffi, Giulia ;
Oni, Tobiloba E. ;
Spielman, Benjamin ;
Hao, Yuan ;
Elyada, Ela ;
Park, Youngkyu ;
Preall, Jonathan ;
Tuveson, David A. .
CANCER DISCOVERY, 2019, 9 (02) :282-301
[24]   Rationale Behind Targeting Fibroblast Activation Protein-Expressing Carcinoma-Associated Fibroblasts as a Novel Chemotherapeutic Strategy [J].
Brennen, W. Nathaniel ;
Isaacs, John T. ;
Denmeade, Samuel R. .
MOLECULAR CANCER THERAPEUTICS, 2012, 11 (02) :257-266
[25]   Transcriptome analysis of human hepatic and pancreatic stellate cells: organ-specific variations of a common transcriptional phenotype [J].
Buchholz, M ;
Kestler, HA ;
Holzmann, K ;
Ellenrieder, V ;
Schneiderhan, W ;
Siech, M ;
Adler, G ;
Bachem, MG ;
Gress, TM .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2005, 83 (10) :795-805
[26]   Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer [J].
Buscail, Louis ;
Bournet, Barbara ;
Cordelier, Pierre .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2020, 17 (03) :153-168
[27]   Revisiting the hallmarks of cancer: The role of hyaluronan [J].
Caon, Ilaria ;
Bartolini, Barbara ;
Parnigoni, Arianna ;
Carava, Elena ;
Moretto, Paola ;
Viola, Manuela ;
Karousou, Evgenia ;
Vigetti, Davide ;
Passi, Alberto .
SEMINARS IN CANCER BIOLOGY, 2020, 62 :9-19
[28]   Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer [J].
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. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (36) :4284-+
[29]   Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels [J].
Chauhan, Vikash P. ;
Martin, John D. ;
Liu, Hao ;
Lacorre, Delphine A. ;
Jain, Saloni R. ;
Kozin, Sergey V. ;
Stylianopoulos, Triantafyllos ;
Mousa, Ahmed S. ;
Han, Xiaoxing ;
Adstamongkonkul, Pichet ;
Popovic, Zoran ;
Huang, Peigen ;
Bawendi, Moungi G. ;
Boucher, Yves ;
Jain, Rakesh K. .
NATURE COMMUNICATIONS, 2013, 4
[30]   Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer [J].
Chen, Yang ;
Yang, Sujuan ;
Tavormina, Jena ;
Tampe, Desiree ;
Zeisberg, Michael ;
Wang, Huamin ;
Mahadevan, Krishnan K. ;
Wu, Chang-Jiun ;
Sugimoto, Hikaru ;
Chang, Chia-Chi ;
Jenq, Robert R. ;
McAndrews, Kathleen M. ;
Kalluri, Raghu .
CANCER CELL, 2022, 40 (08) :818-+