Modeling pancreatic cancer in mice for experimental therapeutics

Mallya, Kavita; Gautam, Shailendra K.; Aithal, Ashwini P; Batra, Surinder K.; Jain, Maneesh

doi:10.1016/j.bbcan.2021.188554

Cited by 52 publications

(48 citation statements)

References 284 publications

(334 reference statements)

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“…Therefore, it was reassuring to demonstrate that HIF2 inhibition with PT2399 enhanced immune responses in our syngeneic pancreatic cancer models. It will be important to evaluate immune responses in autochthonous tumor models that contain higher stromal abundance, 48 and we posit that with higher CAF content, the immune responses to HIF2 inhibition will be more robust. Belzutifan (PT2977, MK6487) is a second-generation HIF2 inhibitor that recently received approval from the Food and Drug Administration for use in von Hippel–Lindau–associated renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment

et al. 2022

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“…However, the timing of animal sacrifice in heterotopic transplantation models is usually determined by humane endpoints defined by local IACUC guidelines. Therefore, survival data obtained from heterotopic transplant models may not accurately reflect tumor burden and associated complications [ 95 ].…”

Section: Target Discovery By Crispr/cas9 Screensmentioning

confidence: 99%

Current applications and future perspective of CRISPR/Cas9 gene editing in cancer

et al. 2022

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Clustered regularly interspaced short palindromic repeats (CRISPR) system provides adaptive immunity against plasmids and phages in prokaryotes. This system inspires the development of a powerful genome engineering tool, the CRISPR/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing system. Due to its high efficiency and precision, the CRISPR/Cas9 technique has been employed to explore the functions of cancer-related genes, establish tumor-bearing animal models and probe drug targets, vastly increasing our understanding of cancer genomics. Here, we review current status of CRISPR/Cas9 gene editing technology in oncological research. We first explain the basic principles of CRISPR/Cas9 gene editing and introduce several new CRISPR-based gene editing modes. We next detail the rapid progress of CRISPR screening in revealing tumorigenesis, metastasis, and drug resistance mechanisms. In addition, we introduce CRISPR/Cas9 system delivery vectors and finally demonstrate the potential of CRISPR/Cas9 engineering to enhance the effect of adoptive T cell therapy (ACT) and reduce adverse reactions.

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“…They are generally classified according to the manner or tumor induction, the site of tumor implantation, and the histopathological characteristics. [178] The first experiments with spontaneous tumor animal models involved the use of a chemical viral induction, or the application of experimental genetic techniques in rats [179] and hamsters. [180] More recent attention has focused on the introduction of oncogenes (especially mutant KRAS genes) into mouse embryonic or somatic cells using transgenic, gene knock-in, and gene knock-out techniques to transfer specific genes into mice via retrovirus.…”

Section: Mouse Modelsmentioning

confidence: 99%

“…Common drawbacks to cell-derived xenografts are the absence of the immune system influence, the lack of genetic and phenotypic heterogeneity offered by immortalized cell lines, the absence of tumor stroma, the risk of alterations during in vitro passages, the infrequent metastasis formation. Part of these limitations have been addressed by coimplantation models using CAFs, and more recently by patient-derived xenografts (PDXs), namely fragments of primary tumors derived from surgical resection [216] and implanted subcutaneously, orthotopically, or under the renal capsule [187,178] in mice. The main advantages of this model are the retention of the morphological characteristics of the parental tumor, the preserved metastatic potential, and the genomic/architectural stability of the obtained xenografts, which make them able to respond to therapy as the original tumor.…”

Section: Mouse Modelsmentioning

confidence: 99%

Multimodal Therapies against Pancreatic Ductal Adenocarcinoma: A Review on Synergistic Approaches toward Ultimate Nanomedicine Treatments

Conte

Cauda

2022

Advanced Therapeutics

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In the last decades, extensive research has been carried out on the understanding and treatment of pancreatic cancer. Despite the significant advances in medicine and nanotechnology, there is an increasing concern about the lack of a standardized therapy with favorable outcomes for patients affected by this malignant disease, whose survival rates are nowadays far alarmingly low. The aim of this review is to offer a comprehensive view on the topic, by drawing upon two strands of research into pancreatic cancer. First, a detailed overview on the tumor genesis, progression, and resulting intricate microenvironment is presented. Thereafter, an extensive insight into the current treatments and their evolution throughout time, with a major focus on nanomedicine approaches, are offered to the reader. With respect to previous studies, a particular emphasis is given here to innovative theranostic approaches. In the light of what is now well established by recent evidence, the focus is given to multimodal treatments involving the combination of different therapies and, in particular, of nanoparticle‐based medicine. The challenging purpose is finally of shedding light on future ultimate treatments out of the currently followed well‐worn paths.

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Modeling pancreatic cancer in mice for experimental therapeutics

Cited by 52 publications

References 284 publications

Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment

Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment

Current applications and future perspective of CRISPR/Cas9 gene editing in cancer

Multimodal Therapies against Pancreatic Ductal Adenocarcinoma: A Review on Synergistic Approaches toward Ultimate Nanomedicine Treatments

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