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BxPC-3: Evaluating responses to standard therapeutic agents in subcutaneous mouse model of human pancreatic cancer

1 February 2024

Author: Gunisha Arora, Medical and Scientific Writer, Scientific Development
Date: February, 2024
 

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Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), stands as a formidable global health challenge with a projected incidence of 18.6 per 100,000 by 2050. Surgical resection, the potential cure, is hindered by late-stage diagnoses, limiting viable candidates. Accounting for 85% of pancreatic cancer cases, PDAC often eludes early detection due to its retroperitoneal location, resulting in dismal 5-year survival rates not surpassing 10%. Other challenges include the tumor’s aggressive nature, patient frailty and pervasive resistance to therapies. Overcoming these challenges demands innovative approaches and BxPC-3, a human PDAC model, emerges as a valuable tool for in vitro and in vivo testing of novel therapeutic interventions to improve outcomes.

Derived from a 61-year-old Caucasian female with pancreatic adenocarcinoma, the BxPC-3 model exhibits striking parallels to the patient’s primary tumor when grown in nude mice. The cell line lacks tumor suppressors CDKN2A/p16 and SMAD4/DPC4 due to homozygous deletions, possesses a TP53 missense mutation and maintains a wild-type RAS configuration. Displaying consistently elevated levels of pro-angiogenic factors such as IL-1α and IL-8, BxPC-3 suggests a notable angiogenic potential.1 Retaining an epithelial morphology, the model exhibits impaired TGFβ signaling. BxPC-3 tumors showcase distinct fibrosis coupled with the presence of pancreatic stem cells; additionally, the tumors present sizable necrotic areas, indicative of a highly malignant phenotype.2 

At Labcorp, we have run numerous studies using the BxPC-3 model of human pancreatic cancer in the subcutaneous (SC) setting in the NSG and NSG-dKO mouse models with multiple standard agents, vehicles and mode of deliveries. 

Growth of subcutaneously implanted BxPC-3 cells in NSG mice across different studies show reproducibility with high latency periods before tumor development.


 

Study 1

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Figure 1: Growth kinetics of BxPC-3, 1.00+007 cells/animal subcutaneously implanted in NSG mice observed in multiple studies

Figure 1: Growth kinetics of BxPC-3, 1.00+007 cells/animal subcutaneously implanted in NSG mice observed in multiple studies

Study 2

BxPC-3 growth of SC high-axilla implant was reproducible in NSG and dKO mouse models at both concentrations of 5.00E+006 cells and 1.00E+007 cells.

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Figure 2: Growth kinetics in the NSG and NSG-dKO mouse models.

Figure 2: Growth kinetics in the NSG and NSG-dKO mouse models.

Response to standard of care agents

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Figure 3: Response of BxPC-3 SC high axilla implant model to gemcitabine, paclitaxel, 5-fluorouracil and cisplatin. A) Mean tumor burden ± SE. B) Percent body weight change ± SE. C) Percent progression-free survival (PFS is plotted using time to progression or time on study) by group.

Figure 3: Response of BxPC-3 SC high axilla implant model to gemcitabine, paclitaxel, 5-fluorouracil and cisplatin. A) Mean tumor burden ± SE. B) Percent body weight change ± SE. C) Percent progression-free survival (PFS is plotted using time to progression or time on study) by group.

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Figure 4: Response of BxPC-3 SC high axilla tumor fragment implant model to erlotinib, icotinib and docetaxel. A) Mean tumor burden ± SE. B) Percent body weight change ± SE.

Figure 4: Response of BxPC-3 SC high axilla tumor fragment implant model to erlotinib, icotinib and docetaxel. A) Mean tumor burden ± SE. B) Percent body weight change ± SE.

As in the clinical response to standard of care, treatment response preclinically is highly dependent on the tumor line being used. There are many factors that can contribute to the responsiveness or lack thereof to treatment. However, looking across several different tumor lines within the same indication can provide key information about how effective a new therapy may be in the clinic. 

Labcorp has multiple pancreatic cancer cell lines available for use. View our cell line list or contact us to run your next pancreatic cancer study.

Contact us to learn more about how our subcutaneous, metastatic and orthotopic models coupled with our ex vivo analysis services can be used to advance your preclinical research.

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