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

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 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 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 The timing and design of stereotactic radiotherapy approaches as a part of neoadjuvant therapy in pancreatic cancer: Is it time for change?

2021 ◽  
Vol 28 ◽  
pp. 124-128
Author(s):  
Jeffrey M. Ryckman ◽  
Bradley N. Reames ◽  
Kelsey A. Klute ◽  
William A. Hall ◽  
Michael J. Baine ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Stereotactic Radiotherapy

scholarly journals Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma—Who Will Benefit from a Secondary Resection?

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 77
Author(s):  
Nathalie Rosumeck ◽  
Lea Timmermann ◽  
Fritz Klein ◽  
Marcus Bahra ◽  
Sebastian Stintzig ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Induction Therapy ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Comprehensive Cancer Center ◽  
Secondary Resection ◽  
Number Of Patients

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

Machine learning-based auto-segmentation of histological residual tumor in resected pancreatic cancer after neoadjuvant therapy

Pancreatology ◽  
2021 ◽  
Vol 21 ◽  
pp. S90
Author(s):  
B. Janssen ◽  
R. Theijse ◽  
S. van Roessel ◽  
R. de Ruiter ◽  
A. Berkel ◽  
...  
Keyword(s):  
Machine Learning ◽  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Residual Tumor

scholarly journals Neoadjuvant Therapy of Pancreatic Cancer: The Emerging Paradigm?

2012 ◽  
Vol 17 (2) ◽  
pp. 192-200 ◽  
Author(s):  
Kian‐Huat Lim ◽  
Eugene Chung ◽  
Adeel Khan ◽  
Dengfeng Cao ◽  
David Linehan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy
Sign in / Sign up

Export Citation Format

Share Document