Epithelial-Stromal Interactions in Pancreatic Cancer

2019 ◽  
Vol 81 (1) ◽  
pp. 211-233 ◽  
Author(s):  
Yaqing Zhang ◽  
Howard C. Crawford ◽  
Marina Pasca di Magliano
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Lymphatic Vessels ◽  
Cancer Microenvironment ◽  
Cancer Stroma ◽  
The Past ◽  
Overwhelming Evidence ◽  
Cancer Initiation ◽  
Active Research

Pancreatic cancer is characterized by an extensive fibroinflammatory reaction that includes immune cells, fibroblasts, extracellular matrix, vascular and lymphatic vessels, and nerves. Overwhelming evidence indicates that the pancreatic cancer microenvironment regulates cancer initiation, progression, and maintenance. Pancreatic cancer treatment has progressed little over the past several decades, and the prognosis remains one of the worst for any cancer. The contribution of the microenvironment to carcinogenesis is a key area of research, offering new potential targets for treating the disease. Here, we explore the composition of the pancreatic cancer stroma, discuss the network of interactions between different components, and describe recent attempts to target the stroma therapeutically. We also discuss current areas of active research related to the tumor microenvironment.

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ming Jia ◽  
Dan Zhang ◽  
Chunxiang Zhang ◽  
Chunhong Li
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Malignant Tumors ◽  
Treatment Strategies ◽  
Delivery Systems ◽  
Cancer Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Hypoxic Environment ◽  
Promising Therapeutic Approach

AbstractPancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

scholarly journals Pancreatic Cancer Microenvironment and Cellular Composition: Current Understandings and Therapeutic Approaches

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5028
Author(s):  
Linh-Huyen Truong ◽  
Siim Pauklin
Keyword(s):  
Immune Cells ◽  
Ductal Adenocarcinoma ◽  
Cancer Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Therapeutic Approaches ◽  
The Past ◽  
Mechanistic Insight ◽  
Human Solid Tumors ◽  
Main Barrier ◽  
A Current

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human solid tumors, despite great efforts in improving therapeutics over the past few decades. In PDAC, the distinct characteristic of the tumor microenvironment (TME) is the main barrier for developing effective treatments. PDAC TME is characterized by a dense stroma, cancer-associated fibroblasts, and immune cells populations that crosstalk to the subpopulations of neoplastic cells that include cancer stem cells (CSCs). The heterogeneity in TME is also exhibited in the diversity and dynamics of acellular components, including the Extracellular matrix (ECM), cytokines, growth factors, and secreted ligands to signaling pathways. These contribute to drug resistance, metastasis, and relapse in PDAC. However, clinical trials targeting TME components have often reported unexpected results and still have not benefited patients. The failures in those trials and various efforts to understand the PDAC biology demonstrate the highly heterogeneous and multi-faceted TME compositions and the complexity of their interplay within TME. Hence, further functional and mechanistic insight is needed. In this review, we will present a current understanding of PDAC biology with a focus on the heterogeneity in TME and crosstalk among its components. We also discuss clinical challenges and the arising therapeutic opportunities in PDAC research.

scholarly journals Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility

2016 ◽  
Vol 372 (2) ◽  
pp. 210-218 ◽  
Author(s):  
Masafumi Sada ◽  
Kenoki Ohuchida ◽  
Kohei Horioka ◽  
Takashi Okumura ◽  
Taiki Moriyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Cell Motility ◽  
Cancer Cell ◽  
Stellate Cells ◽  
Cancer Cell Motility ◽  
Cancer Stroma ◽  
Fiber Organization

scholarly journals Neoadjuvant Therapy Remodels the Pancreatic Cancer Microenvironment via Depletion of Protumorigenic Immune Cells

2019 ◽  
Vol 26 (1) ◽  
pp. 220-231 ◽  
Author(s):  
Carmen Mota Reyes ◽  
Steffen Teller ◽  
Alexander Muckenhuber ◽  
Björn Konukiewitz ◽  
Okan Safak ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Immune Cells ◽  
Cancer Microenvironment

scholarly journals Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 987
Author(s):  
Andreas Domen ◽  
Delphine Quatannens ◽  
Sara Zanivan ◽  
Christophe Deben ◽  
Jonas Van Audenaerde ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Growth Factors ◽  
Cancer Metastasis ◽  
Therapy Resistance ◽  
Cancer Therapies ◽  
Cancer Associated Fibroblasts ◽  
Novel Therapies ◽  
The Past ◽  
Drug Access

Cancer arises from mutations accruing within cancer cells, but the tumor microenvironment (TME) is believed to be a major, often neglected, factor involved in therapy resistance and disease progression. Cancer-associated fibroblasts (CAFs) are prominent and key components of the TME in most types of solid tumors. Extensive research over the past decade revealed their ability to modulate cancer metastasis, angiogenesis, tumor mechanics, immunosuppression, and drug access through synthesis and remodeling of the extracellular matrix and production of growth factors. Thus, they are considered to impede the response to current clinical cancer therapies. Therefore, targeting CAFs to counteract these protumorigenic effects, and overcome the resistance to current therapeutic options, is an appealing and emerging strategy. In this review, we discuss how CAFs affect prognosis and response to clinical therapy and provide an overview of novel therapies involving CAF-targeting agents in lung and pancreatic cancer.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

Cirurgia Paliativa em Pacientes com Tumor Periampular Irressecável: Estudo Retrospectivo de 5 Anos em um Hospital em São José dos Campos – SP/Surgical Palliation in Patients with Unresectable Periampullary Tumor: a Retrospective Study of 5 Years in a Hosp

1970 ◽  
Vol 3 (4) ◽  
pp. 9-20
Author(s):  
José Henrique Gomes Torres ◽  
Rosyane Rena De Freitas
Keyword(s):  
Pancreatic Cancer ◽  
Retrospective Study ◽  
Survival Rates ◽  
Periampullary Tumor ◽  
The Past ◽  
Palliative Procedure ◽  
Surgical Palliation ◽  
Head Of The Pancreas ◽  
Keywords Pancreatic Cancer ◽  
Main Complication

Objetivo: Avaliar diferentes métodos paliativos quanto a sua resolução, complicações e sobrevida em pacientes com tumor periampular irressecável. Materiais e métodos: Estudo retrospectivo com análise dos prontuários de pacientes com tumor periampular irressecável e que foram submetidos a procedimento paliativo no Hospital Municipal Dr José de Carvalho Florence nos últimos cinco anos. Resultados: O principal tumor periampular foi o de cabeça de pâncreas, com incidência de 94%, acometendo pacientes com média de 66 anos, sem preferência por sexo. Os procedimentos mais realizados foram derivação biliar e colocação de endoprótese através de colangiopancreatografia endoscópica retrógrada, apresentando sobrevidas de 586 e 56 dias, respectivamente. Conclusão: A coledocojejunostomia foi o procedimento mais realizado e apresentou menor tempo de internação e maiores sobrevida e tempo de permanência anictérico. Pneumonia foi a complicação mais frequente.  Palavras chave: Câncer pancreático, Colangiocarcinoma, Cuidados paliativos.  Objective: To evaluate different palliative methods concerning its resolution, complications and survival in patients with unresectable periampular tumor. Materials and methods: Retrospective study analysing records of patients with unresectable periampullary tumor and who underwent palliative procedure in the Hospital Municipal Dr José de Carvalho Florence in the past five years. Results: The main periampullary tumor was the head of the pancreas, with an incidence of 94%, affecting patients with an average of 66 years old, regardless of gender. The most common procedures were bypass and biliary stent, with survival rates of 586 and 56 days, respectively. Conclusion: Coledocojejunostomy was the procedure which was the most often performed and showed a shorter hospital stay and longer survival time and time without jaundice. Pneumonia was the main complication.  Keywords: Pancreatic cancer, Cholangiocarcinoma, Palliative care  

scholarly journals NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuan Wang ◽  
Jun Cai ◽  
Lei Zhao ◽  
Dejun Zhang ◽  
Guojie Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Bioinformatics Analysis ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Self Renewal ◽  
Tumor Relapse ◽  
The Past ◽  
Overwhelming Evidence ◽  
Novel Therapeutic Strategies

AbstractExperimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.

scholarly journals Recent Advances in bis-Chalcone-Based Photoinitiators of Polymerization: From Mechanistic Investigations to Applications

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3192
Author(s):  
Nicolas Giacoletto ◽  
Frédéric Dumur
Keyword(s):  
Free Radical ◽  
Radical Polymerization ◽  
Cationic Polymerization ◽  
Free Radical Polymerization ◽  
Research Field ◽  
4D Printing ◽  
Unique Structure ◽  
The Past ◽  
Mechanistic Investigations ◽  
Active Research

Over the past several decades, photopolymerization has become an active research field, and the ongoing efforts to develop new photoinitiating systems are supported by the different applications in which this polymerization technique is involved—including dentistry, 3D and 4D printing, adhesives, and laser writing. In the search for new structures, bis-chalcones that combine two chalcones’ moieties within a unique structure were determined as being promising photosensitizers to initiate both the free-radical polymerization of acrylates and the cationic polymerization of epoxides. In this review, an overview of the different bis-chalcones reported to date is provided. Parallel to the mechanistic investigations aiming at elucidating the polymerization mechanisms, bis-chalcones-based photoinitiating systems were used for different applications, which are detailed in this review.

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