From Genetic Alterations to Tumor Microenvironment: The Ariadne's String in Pancreatic Cancer

被引：27

作者：

Bazzichetto, Chiara ^{[1
]}

Conciatori, Fabiana ^{[1
]}

Luchini, Claudio ^{[2
]}

Simionato, Francesca ^{[3
]}

Santoro, Raffaela ^{[4
]}

Vaccaro, Vanja ^{[1
]}

Corbo, Vincenzo ^{[5
]}

Falcone, Italia ^{[1
]}

Ferretti, Gianluigi ^{[1
]}

Cognetti, Francesco ^{[1
]}

Melisi, Davide ^{[4
]}

Scarpa, Aldo ^{[5
]}

Ciuffreda, Ludovica ^{[6
]}

Milella, Michele ^{[3
]}

机构：

[1] IRCCS Regina Elena Natl Canc Inst, Med Oncol 1, I-00144 Rome, Italy

[2] Univ & Hosp Trust Verona, Sect Pathol, Dept Diagnost & Publ Hlth, I-37134 Verona, Italy

[3] Univ Verona, Div Oncol, I-37126 Verona, Italy

[4] Univ Verona, Med Digest Mol Clin Oncol Res Unit, I-37126 Verona, Italy

[5] Univ & Hosp Trust Verona, ARC Net Res Ctr, I-37126 Verona, Italy

[6] IRCCS Regina Elena Natl Canc Inst, Dept Res Adv Diagnost & Technol Innovat, SAFU, I-00144 Rome, Italy

来源：

CELLS | 2020年 / 9卷 / 02期

关键词：

pancreatic cancer; oncogene; tumor suppressor; signaling pathway; tumor microenvironment; targeted therapy; GROWTH-FACTOR-BETA; NF-KAPPA-B; PAPILLARY MUCINOUS NEOPLASM; NECROSIS-FACTOR-ALPHA; EPITHELIAL-MESENCHYMAL TRANSITION; STELLATE CELLS; TGF-BETA; SUPPRESSOR-CELLS; K-RAS; EXTRACELLULAR-MATRIX;

D O I：

10.3390/cells9020309

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The threatening notoriety of pancreatic cancer mainly arises from its negligible early diagnosis, highly aggressive progression, failure of conventional therapeutic options and consequent very poor prognosis. The most important driver genes of pancreatic cancer are the oncogene KRAS and the tumor suppressors TP53, CDKN2A, and SMAD4. Although the presence of few drivers, several signaling pathways are involved in the oncogenesis of this cancer type, some of them with promising targets for precision oncology. Pancreatic cancer is recognized as one of immunosuppressive phenotype cancer: it is characterized by a fibrotic-desmoplastic stroma, in which there is an intensive cross-talk between several cellular (e.g., fibroblasts, myeloid cells, lymphocytes, endothelial, and myeloid cells) and acellular (collagen, fibronectin, and soluble factors) components. In this review; we aim to describe the current knowledge of the genetic/biological landscape of pancreatic cancer and the composition of its tumor microenvironment; in order to better direct in the intrinsic labyrinth of this complex tumor type. Indeed; disentangling the genetic and molecular characteristics of cancer cells and the environment in which they evolve may represent the crucial step towards more effective therapeutic strategies

引用

页数：34

共 252 条

[1]

Ademmer K, 1998, CLIN EXP IMMUNOL, V112, P21

[2] The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance [J].

Ahmed, Sunjida ;

Bradshaw, Azore-Dee ;

Gera, Shweta ;

Dewan, M. Zahidunnabi ;

Xu, Ruliang .

JOURNAL OF CLINICAL MEDICINE, 2017, 6 (01)

[3] MOST HUMAN CARCINOMAS OF THE EXOCRINE PANCREAS CONTAIN MUTANT C-K-RAS GENES [J].

ALMOGUERA, C ;

SHIBATA, D ;

FORRESTER, K ;

MARTIN, J ;

ARNHEIM, N ;

PERUCHO, M .

CELL, 1988, 53 (04) :549-554

[4] Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas [J].

Amato, Eliana ;

dal Molin, Marco ;

Mafficini, Andrea ;

Yu, Jun ;

Malleo, Giuseppe ;

Rusev, Borislav ;

Fassan, Matteo ;

Antonello, Davide ;

Sadakari, Yoshihiko ;

Castelli, Paola ;

Zamboni, Giuseppe ;

Maitra, Anirban ;

Salvia, Roberto ;

Hruban, Ralph H. ;

Bassi, Claudio ;

Capelli, Paola ;

Lawlor, Rita T. ;

Goggins, Michael ;

Scarpa, Aldo .

JOURNAL OF PATHOLOGY, 2014, 233 (03) :217-227

[5] Secretion of fibronectin by human pancreatic stellate cells promotes chemoresistance to gemcitabine in pancreatic cancer cells [J].

Amrutkar, Manoj ;

Aasrum, Monica ;

Verbeke, Caroline S. ;

Gladhaug, Ivar P. .

BMC CANCER, 2019, 19 (1)

[6] Clinicopathological correlates of pancreatic intraepithelial neoplasia: A comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma [J].

Andea, A ;

Sarkar, F ;

Adsay, VN .

MODERN PATHOLOGY, 2003, 16 (10) :996-1006

[7] Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors [J].

Andricovich, Jaclyn ;

Perkail, Stephanie ;

Kai, Yan ;

Casasanta, Nicole ;

Peng, Weiqun ;

Tzatsos, Alexandros .

CANCER CELL, 2018, 33 (03) :512-+

[8]

[Anonymous], 2019, LUSO ANTIBIOTICI ITA

[9]

[Anonymous], NAT REV IMMUNOL

[10] Pancreatic stellate cells: a starring role in normal and diseased pancreas [J].

Apte, Minoti V. ;

Pirola, Romano C. ;

Wilson, Jeremy S. .

FRONTIERS IN PHYSIOLOGY, 2012, 3

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