Progress in Animal Models of Pancreatic Ductal Adenocarcinoma

Kong, Kaiwen; Guo, Meng; Liu, Yanfang; Zheng, Jianming

doi:10.7150/jca.37529

Cited by 43 publications

(39 citation statements)

References 93 publications

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“…In addition to chemical and genetic induction of mutation, an animal model of pancreatic cancer can also be achieved by injection of pancreatic cancer cells, either patient-derived or well-established cell lines, into nude mice or severe combined immunodeficient (SCID) mice, allowing the pancreatic cancer cells from human origin to develop into a tumor in vivo [ 58 , 59 , 60 , 61 ]. Similar to the former case, a patient-derived xenograft (PDX) model can be derived by transplanting a patient-derived tumor fragment into an SCID mouse [ 62 ].…”

Section: Animal Models For Studying Pdac Progressionmentioning

confidence: 99%

Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate

Chang

Lin

2021

Bioengineering

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Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and has seen only modest improvements in patient survival rate over the past few decades. PDAC is highly aggressive and resistant to chemotherapy, owing to the presence of a dense and hypovascularized fibrotic tissue, which is composed of stromal cells and extracellular matrices. Increase deposition and crosslinking of matrices by stromal cells lead to a heterogeneous microenvironment that aids in PDAC development. In the past decade, various hydrogel-based, in vitro tumor models have been developed to mimic and recapitulate aspects of the tumor microenvironment in PDAC. Advances in hydrogel chemistry and engineering should provide a venue for discovering new insights regarding how matrix properties govern PDAC cell growth, migration, invasion, and drug resistance. These engineered hydrogels are ideal for understanding how variation in matrix properties contributes to the progressiveness of cancer cells, including durotaxis, the directional migration of cells in response to a stiffness gradient. This review surveys the various hydrogel-based, in vitro tumor models and the methods to generate gradient stiffness for studying migration and other cancer cell fate processes in PDAC.

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Section: Animal Models For Studying Pdac Progressionmentioning

confidence: 99%

Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate

Chang

Lin

2021

Bioengineering

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“…Despite the importance of mouse models, these models do not fully reflect human disease. Moreover, they have limitations such as differences in size, macroscopic pancreatic organization, and immunity [ 17 , 28 ]. Therefore, pancreatic cancer research requires a new animal model that is more similar to humans.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, only 5–8% of anticancer drugs that have entered clinical trials from preclinical studies are approved for clinical use [ 15 ]. Therefore, large animals have received considerable attention as potential alternative models of pancreatic cancer [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-RasG12D

Yang

Song

Sim

et al. 2020

IJMS

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In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans. Therefore, large animals may be more useful for the investigation of pancreatic cancer. Pigs have recently emerged as a new model of pancreatic cancer due to their similarities to humans, but no pig pancreatic cancer cell lines have been established for use in drug screening or analysis of tumor biology. Here, we established and characterized an immortalized miniature pig pancreatic cell line derived from primary pancreatic cells and pancreatic cancer-like cells expressing K-rasG12D regulated by the human PTF1A promoter. Using this immortalized cell line, we analyzed the gene expression and phenotypes associated with cancer cell characteristics. Notably, we found that acinar-to-ductal transition was caused by K-rasG12D in the cell line constructed from acinar cells. This may constitute a good research model for the analysis of acinar-to-ductal metaplasia in human pancreatic cancer.

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“…Murine models for human PDAC research are useful tools as mice and humans have comparable anatomic, cellular, and genomic features, including tumor biology [ 80 ]. For the scope of this review, we will focus on murine-based in vivo model systems, however in vivo PDAC models from alternative species are also used, and we refer to these excellent articles [ 81 , 82 ].…”

Section: Overview Of Common Experimental Models To Study Ov Therapmentioning

confidence: 99%

Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

Holbrook

Goad

Grdzelishvili

2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. However, some PDAC cell lines are resistant to VSV. Upregulated type I IFN signaling and constitutive expression of a subset of interferon-simulated genes (ISGs) play a major role in such resistance, while other mechanisms, such as inefficient viral attachment and resistance to VSV-mediated apoptosis, also play a role in some PDACs. Several alternative approaches have been shown to break the resistance of PDACs to VSV without compromising VSV oncoselectivity, including (i) combinations of VSV with JAK1/2 inhibitors (such as ruxolitinib); (ii) triple combinations of VSV with ruxolitinib and polycations improving both VSV replication and attachment; (iii) combinations of VSV with chemotherapeutic drugs (such as paclitaxel) arresting cells in the G2/M phase; (iv) arming VSV with p53 transgenes; (v) directed evolution approach producing more effective OVs. The latter study demonstrated impressive long-term genomic stability of complex VSV recombinants encoding large transgenes, supporting further clinical development of VSV as safe therapeutics for PDAC.

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Progress in Animal Models of Pancreatic Ductal Adenocarcinoma

Cited by 43 publications

References 93 publications

Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate

Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate

Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-RasG12D

Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

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