Stromal biology and therapy in pancreatic cancer : ready for clinical translation?
Albrecht Neesse,Christian Bauer,Daniel Öhlund,Matthias Lauth,Malte Buchholz,Patrick Michl,David A. Tuveson,Thomas M. Gress +7 more
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TLDR
An update of the most recent findings in the tumour microenvironment in PDA is provided and their translational and clinical implications for basic scientists and clinicians alike are discussed.Abstract:
Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.read more
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Journal ArticleDOI
Cancer-associated fibroblasts in gastrointestinal cancer
Hiroki Kobayashi,Atsushi Enomoto,Susan L. Woods,Alastair D. Burt,Masahide Takahashi,Daniel L. Worthley +5 more
TL;DR: An improved understanding of CAF biology could lead to the development of novel stroma-based diagnostics, prognostics and therapeutics, and the clinical implications of CAFs as biomarkers and potential targets for prevention and treatment of patients with gastrointestinal cancer are discussed.
Journal ArticleDOI
CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer.
Brooke A. Pereira,Claire Vennin,Michael Papanicolaou,Cecilia R. Chambers,Cecilia R. Chambers,David Herrmann,David Herrmann,Jennifer P. Morton,Thomas R. Cox,Thomas R. Cox,Paul Timpson,Paul Timpson +11 more
TL;DR: This review explores how different aspects of CAF heterogeneity are defined and how these manifest in multiple cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC).
Journal ArticleDOI
Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis
Yasuyuki Mizutani,Hiroki Kobayashi,Hiroki Kobayashi,Tadashi Iida,Naoya Asai,Atsushi Masamune,Akitoshi Hara,Nobutoshi Esaki,Kaori Ushida,Shinji Mii,Yukihiro Shiraki,Kenju Ando,Liang Weng,Seiichiro Ishihara,Suzanne M. Ponik,Matthew W. Conklin,Hisashi Haga,Arata Nagasaka,Takaki Miyata,Makoto Matsuyama,Tomoe Kobayashi,Tsutomu Fujii,Suguru Yamada,Junpei Yamaguchi,Tongtong Wang,Susan L. Woods,Daniel L. Worthley,Teppei Shimamura,Mitsuhiro Fujishiro,Yoshiki Hirooka,Atsushi Enomoto,Masahide Takahashi +31 more
TL;DR: Meflin is a marker of rCAFs that suppress PDAC progression, and in-situ hybridization analysis of 71 human PDAC tissues revealed that the infiltration of Meflin-positive CAFs correlated with favorable patient outcome and a mechanism for generating CAF heterogeneity.
Journal ArticleDOI
The enhancement of glycolysis regulates pancreatic cancer metastasis
TL;DR: In an extremely nutrient-deficient and hypoxic environment resulting from uncontrolled growth, vascular disturbances and desmoplastic reactions, pancreatic cancer cells utilize “metabolic reprogramming” to satisfy their energy demand and support malignant behaviors such as metastasis.
Journal ArticleDOI
Microenvironmental Determinants of Pancreatic Cancer
Elisabeth Hessmann,Soeren M. Buchholz,Ihsan Ekin Demir,Shiv K. Singh,Thomas M. Gress,Volker Ellenrieder,Albrecht Neesse +6 more
TL;DR: Findings suggest that parts of the TME in PDAC may also possess tumor-restraining properties rendering tailored therapies even more challenging, and there is still a large discrepancy between multiple successful preclinical results and subsequent failure in clinical trials.
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