Pancreatic Ductal Adenocarcinoma (PDAC)

Inquiry

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with prominent stromal barrier, restricted drug penetration, and extremely poor prognosis, often called the "king of cancers." Alfa Cytology is a global leader in cancer research. With our extensive experience and advanced platforms, our talented scientists provide one-stop solutions for PDAC animal model development, efficacy evaluation, pancreatic orthotopic model validation, liver metastasis and peritoneal dissemination evaluation, postoperative relapse studies, tumor immunology testing, stroma and fibrosis testing, target expression validation, pathology testing, molecular mechanism testing, and PK/PD, based on client candidate drugs, molecular background, drug type, pancreatic orthotopic microenvironment, metastatic direction, local administration route, immune system requirements, and R&D stages. We also provide zebrafish experimental services and cell-based experimental services, covering diverse research needs from in vitro to in vivo and from high-throughput screening to mechanism validation.

Introduction to Pancreatic Ductal Adenocarcinoma (PDAC)

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor originating from pancreatic ductal epithelium, the most common type of pancreatic cancer, and one of the digestive system malignancies with the worst prognosis. PDAC is characterized by highly fibrotic stroma, low perfusion, significant immunosuppression, and restricted drug penetration. Clinically, PDAC is commonly managed based on resectability, molecular background, and treatment stage. Resectable PDAC is mainly treated with surgery combined with adjuvant chemotherapy; locally advanced and metastatic PDAC relies more on FOLFIRINOX, gemcitabine plus nab-paclitaxel, targeted agents, and immunotherapy. KRAS mutation, BRCA/PALB2/HRD, KRAS wild-type/EGFR dependence, and CA19-9 are important stratification markers in current drug development. Common metastatic routes in PDAC include liver metastasis and peritoneal dissemination. Among these, peritoneal dissemination, ascites formation, and liver metastasis are high-priority scenarios in translational research. The PDAC immune microenvironment is characterized by CAFs, MDSCs, TAMs, and immunosuppressive cytokines, with an overall immune-excluded state.

Fig. 1 PDAC microenvironment and classification. Fig. 1 Overview of pancreatic ductal adenocarcinoma (PDAC): tumor microenvironment and classification. (Akhuba L, et al.; 2022)

Therefore, PDAC animal studies need to be differentially designed based on molecular background, stromal barrier, drug penetration requirement, metastatic direction, immune system requirements, and administration route, in order to better support candidate screening, efficacy evaluation, and clinical translation assessment.

Our Services

Alfa Cytology has established a comprehensive solution platform for liver cancer animal experimental research, built around hepatocellular carcinoma (HCC) early efficacy screening, liver orthotopic microenvironment, intrahepatic dissemination, lung metastasis, chronic disease background carcinogenesis, immunotherapy, anti-angiogenesis combination, local therapy, and relapse/MRD scenarios. Leveraging this integrated platform, Alfa Cytology provides end-to-end services covering the full liver cancer research workflow.

Preclinical Efficacy Studies

Pancreatic ductal adenocarcinoma drug development requires model selection based on KRAS background, DDR status, pancreatic orthotopic stroma, liver metastasis, peritoneal dissemination, and immunosuppressive microenvironment. Alfa Cytology provides integrated animal study solutions, from cell line selection to model validation, for small molecules, KRAS/RAS inhibitors, DDR/PARP agents, ADCs, nanodelivery, local formulations, radiotherapy combination, ablation/interventional combination, immune checkpoint inhibitors, STING, TCEs, CAR-T/NK, and postoperative relapse programs.

In Vitro and In Vivo Layered Validation

Animal studies can evaluate whether a candidate inhibits tumor growth, pancreatic orthotopic burden, liver metastasis, peritoneal dissemination, or postoperative relapse; zebrafish platforms provide high-throughput in vivo screening covering tumor proliferation, pancreatic orthotopic colonization, liver metastasis, peritoneal dissemination, angiogenesis, immune co-culture, and drug toxicity; cell-based experiments validate proliferation, apoptosis, KRAS pathway, DNA damage repair, migration and invasion, CAF co-culture, drug penetration, ADC internalization, and immune killing.

Clinical Relevance Studies

When programs advance to pancreatic orthotopic, drug penetration, liver metastasis, peritoneal dissemination, local therapy, immunotherapy, humanized immunotherapy, or postoperative relapse stages, Alfa Cytology can further provide orthotopic models, metastasis models, peritoneal dissemination models, syngeneic immunocompetent models, humanized immune models, or relapse models to help clients generate evidence more aligned with clinical scenarios.

PDAC Mechanism Research

For PDAC studies, experimental design typically needs to address KRAS pathway, stromal barrier, liver metastasis, peritoneal dissemination, and immunosuppressive microenvironment simultaneously. Alfa Cytology provides model development, dosing intervention, pathology testing, immunology testing, protein testing, and RNA testing services, covering KRAS, pERK/pS6, BRCA/PALB2, CA19-9, CAF, αSMA, collagen, TME remodeling, liver metastasis, and postoperative relapse mechanisms.

Candidate Screening

Early screening typically requires rapid assessment of whether a candidate demonstrates in vivo antitumor signals. Alfa Cytology conducts TGI, RTV, PK/PD, and target evaluations using molecularly matched subcutaneous CDX models, providing data to support dose selection, dosing frequency, and candidate prioritization.

Molecular Mechanism Studies

Depending on program needs, we offer IHC, IF, flow cytometry, ELISA, Western blot, qPCR, RNA-seq, single-cell sequencing, spatial immune analysis, CA19-9, αSMA/collagen testing, liver metastasis pathology, ascites analysis, drug tissue distribution, and PK/PD testing.

For clients with only a candidate drug, target direction, or preliminary mechanistic hypothesis, Alfa Cytology assists in structuring cell line selection, model pathways, group design, dosing regimens, detection endpoints, terminal sample collection, and data presentation，translating R&D questions into executable animal study protocols. Our capabilities support a broad spectrum of therapeutic modalities, including but not limited to:

Supported R&D Programs

R&D Project	Cell Lines	Host System	Preferred Model	Key Endpoints
Early efficacy screening and dose exploration	PANC-1, MiaPaCa-2, AsPC-1, BxPC-3, Capan-1, CFPAC-1	BALB/c nude, NOD-SCID, NSG	Subcutaneous CDX	TGI, RTV, terminal tumor weight, body weight, Ki67, cleaved caspase-3, PK/PD.
KRAS mutation and stromal-type programs	PANC-1, MiaPaCa-2, MiaPaCa-2-luc	BALB/c nude, NOD-SCID, NSG	KRAS-mutant subcutaneous CDX for early screening, pancreatic orthotopic model for confirmation	KRAS mutation background, pERK, pS6, TGI, drug tissue distribution, αSMA, collagen.
BRCA/PALB2/DDR programs	Capan-1, CFPAC-1	BALB/c nude, NOD-SCID, NSG	DDR background CDX for early screening, orthotopic or relapse models for deeper evaluation	DNA damage, γH2AX, RAD51, platinum response, PARP combination, time to relapse, PK/PD.
KRAS wild-type / EGFR-dependent programs	BxPC-3, BxPC-3-luc	BALB/c nude, NOD-SCID, NSG	KRAS wild-type CDX for early screening, orthotopic model for confirmation	EGFR expression, pERK, TGI, target retention, drug internalization, PK/PD.
High-invasion / high-metastasis programs	AsPC-1, AsPC-1-luc, CFPAC-1, MiaPaCa-2-luc	BALB/c nude, NOD-SCID, NSG	High-metastasis CDX for early screening, orthotopic spontaneous or experimental metastasis models for deeper evaluation	Orthotopic expansion, liver metastasis, peritoneal dissemination, BLI, EMT, MMP, survival.
Pancreatic orthotopic microenvironment and drug penetration	PANC-1-luc, MiaPaCa-2-luc, AsPC-1-luc, BxPC-3-luc, Capan-1-luc	NSG, NOD-SCID	Pancreatic orthotopic model	Orthotopic burden, ultrasound/BLI, CA19-9, αSMA, collagen, CD31, drug penetration, survival.
Syngeneic immunocompetent orthotopic research	Pan02/Panc02-luc, KPC-derived cells, KPC-luc	C57BL/6 immunocompetent mice	Pan02/Panc02 or KPC syngeneic orthotopic model	Orthotopic burden, immune infiltration, CD8/FoxP3, myeloid cell profile, TCR repertoire, liver metastasis, survival.
Liver metastasis and liver-targeted delivery	AsPC-1, MiaPaCa-2, MiaPaCa-2-luc; Pan02/Panc02, KPC	BALB/c nude, NSG; C57BL/6 immunocompetent mice	Intrasplenic/portal vein liver metastasis model or orthotopic spontaneous liver metastasis model	Liver metastatic nodule count, liver weight, BLI/imaging, liver histopathology, liver tissue drug concentration, survival.
Peritoneal dissemination and intraperitoneal local therapy	AsPC-1-luc, MiaPaCa-2-luc; Pan02/Panc02-luc, KPC-luc	NSG, NOD-SCID; C57BL/6 immunocompetent mice	Peritoneal dissemination model or orthotopic spontaneous peritoneal dissemination model	Peritoneal nodule count, PCI-like score, ascites volume, intraperitoneal BLI, local drug concentration, survival.
Perioperative therapy / post-resection relapse	AsPC-1-luc, MiaPaCa-2-luc; Pan02/Panc02-luc, KPC-luc	NSG, NOD-SCID; C57BL/6 immunocompetent mice	Pancreatic orthotopic model with post-resection relapse observation	Local relapse, liver metastasis recurrence, peritoneal relapse, BLI, survival, MRD-related markers
Immunotherapy / TME remodeling	Pan02/Panc02, KPC-derived cells	C57BL/6 immunocompetent mice	Syngeneic subcutaneous screening, syngeneic orthotopic model for key validation	CD8/FoxP3, MDSC, macrophages, PD-L1, cytokines, single-cell analysis, survival.
Local delivery / radiotherapy / interventional therapy	PANC-1-luc, MiaPaCa-2-luc, AsPC-1-luc; Pan02/Panc02-luc, KPC-luc	NSG, NOD-SCID; C57BL/6 immunocompetent mice	Pancreatic orthotopic model, with metastasis or relapse models when needed	Local drug distribution, pancreatic tissue exposure, orthotopic burden, fibrosis, local toxicity, survival.
TCE / CAR-T/NK / human immune-dependent therapies	PANC-1, MiaPaCa-2, BxPC-3, AsPC-1, Capan-1 and target-positive models	huPBMC or huHSC-reconstituted NSG/NOG mice	Humanized immune model	hCD45, hCD3, hCD8, hNK, T cell activation, cytokines, CRS/xGvHD risk.
KRAS frontier drugs and downstream combinations	PANC-1, MiaPaCa-2, AsPC-1 and KRAS mutation-confirmed models; KPC model	BALB/c nude, NSG; C57BL/6 immunocompetent mice	KRAS background-matched CDX for early screening, orthotopic and metastasis models for confirmation	KRAS mutation background, pERK, pS6, TGI, orthotopic burden, metastatic burden, PK/PD.

Comprehensive Test and Data Analysis Platform

For pancreatic ductal adenocarcinoma programs focused on stromal barrier and drug penetration evaluation, we configure TGI, RTV, terminal tumor weight, BLI, ultrasound, survival, orthotopic pancreatic burden, liver metastatic nodules, peritoneal nodules, PCI-like score, ascites volume, CA19-9, KRAS pathway, pERK, pS6, αSMA, collagen, and pancreatic tissue exposure, highlighting stromal remodeling, drug penetration, and peritoneal dissemination.

Multimodal In Vivo Imaging

IVIS Spectrum photon bioluminescence quantification for orthotopic pancreatic tumors and peritoneal dissemination tracking
Small-animal ultrasound for orthotopic pancreatic lesions and stromal barrier monitoring
micro-CT 3D reconstruction for liver metastasis and peritoneal lesion assessment

Pathology and IHC/IF Staining

KRAS / pERK / pS6 pathway and CA19-9 assessment
αSMA / collagen / FAP stroma and fibrosis assessment
mIF multiplex immunofluorescence for in situ target and PDAC TME quantification

TME Microenvironment and Immune Profiling

CD8 / FoxP3 infiltration ratio and CAF subset analysis
MDSC and myeloid-derived suppressive cell profiling
Cytokine storm (IFN-γ / IL-6) CBA suspension array

Access Our PDAC Model Library

PDAC Cell Line Panel

Alfa Cytology's PDAC cell line panel covers KRAS mutation and downstream pathways, BRCA/PALB2-related DDR deficiency, KRAS wild-type/EGFR dependence, stromal barrier and drug penetration, and immuno-oncology, enabling cell line selection and matching based on molecular background, pathway readouts, stromal characteristics, and immune system requirements.

KRAS Mutation and Stromal-Type Representative Cell Lines

PANC-1: a commonly used PDAC model in KRAS mutation, stromal-type, and high-invasion backgrounds, suitable for KRAS pathway, small molecules, nanodelivery, CAF interaction, EMT, and local therapy early screening.
MiaPaCa-2: suitable for KRAS mutation, small molecules, local therapy, and orthotopic expansion research; MiaPaCa-2-luc can be used for pancreatic orthotopic, liver metastasis, and peritoneal dissemination model escalation.
KRAS programs need to clarify mutation background and pathway readouts; subcutaneous tumor shrinkage only indicates basic activity and cannot substitute for pERK/pS6 inhibition, orthotopic penetration, liver metastasis control, and long-term relapse validation.

Secretory and DDR-Related Representative Cell Lines

Capan-1: a high-priority model in BRCA2-related and DDR research, suitable for platinum sensitivity, PARP inhibitors, DNA damage repair, maintenance therapy, and long-term dosing research.
CFPAC-1: commonly used for secretory-type and high-metastasis direction supplementary research, and can also be used for DDR, metastasis, and local delivery program model combinations.
DDR programs should detect DNA damage, γH2AX, RAD51, and platinum response; if the program is positioned for maintenance therapy, long-term dosing, withdrawal observation, or post-resection relapse models should be entered.

KRAS Wild-Type and EGFR-Dependent Cell Lines

BxPC-3: a representative model for KRAS wild-type and EGFR-dependent directions, suitable for EGFR antibodies, bispecifics, ADCs, partial cytotoxic agents, and target antigen expression stability research.
BxPC-3 cannot represent the mainstream KRAS-mutant PDAC background; if the program is KRAS inhibition or KRAS downstream combination, it should not be the sole model.

High-Metastasis Representative Cell Lines

AsPC-1: suitable for high-metastasis, liver metastasis, peritoneal dissemination, local delivery, and advanced disease course research; AsPC-1-luc is suitable for dynamic tracking of orthotopic burden, liver metastasis, and peritoneal dissemination.
MiaPaCa-2 combines KRAS mutation background and good orthotopic expansion capacity, suitable for orthotopic validation and metastasis early research; CFPAC-1 can serve as a high-metastasis and secretory background supplementary model.
Metastasis programs cannot only look at subcutaneous TGI; if the program claims anti-metastasis or anti-dissemination, at least liver metastasis, peritoneal dissemination, or orthotopic spontaneous metastasis endpoints should be configured.

Syngeneic Immunocompetent Model Representative Lines

Pan02/Panc02: can establish syngeneic subcutaneous, syngeneic orthotopic, and dissemination models in C57BL/6 mice, suitable for immune checkpoint, STING, cytokines, TME remodeling, and local therapy research.
KPC-derived cells: better reflect KRAS/TP53-driven PDAC biology, suitable for immunotherapy, orthotopic models, metastasis, relapse, and highly fibrotic microenvironment research; KPC-luc is suitable for long-term dynamic tracking.
Syngeneic models retain the intact immune system, but murine tumors differ from human tumors; human target agents, TCE, CAR-T/NK, and specific human antibodies still require human CDX or humanized model supplementary validation.

PDAC Animal Model Panel

Alfa Cytology provides end-to-end PDAC animal model development services, spanning model design, cell line selection, model construction, dosing intervention, efficacy evaluation, pathology, immunology, molecular mechanism testing, and PK/PD analysis. The models below represent our core capabilities across KRAS mutation and downstream pathways, BRCA/PALB2-related DDR deficiency, KRAS wild-type/EGFR dependence, pancreatic orthotopic stromal barrier, low perfusion and drug penetration, liver metastasis, peritoneal dissemination, perioperative therapy, local delivery, immunotherapy, humanized immunotherapy, and postoperative relapse/MRD research. Each model can be customized to match your program's molecular background, drug type, pancreatic orthotopic microenvironment, metastatic direction, local administration route, immune system requirements, and R&D stage, from early screening to clinical relevance validation.

Subcutaneous Xenograft Model (CDX)

Subcutaneous CDX typically involves inoculating human PDAC cells subcutaneously into immunodeficient mice, followed by randomization and dosing once tumors reach a predetermined volume. Commonly used hosts include BALB/c nude, NOD-SCID, and NSG mice. Commonly used cell lines include PANC-1, MiaPaCa-2, AsPC-1, BxPC-3, Capan-1, and CFPAC-1.

Model characteristics
PANC-1 and MiaPaCa-2 are suitable for KRAS pathway, small molecules, nanodelivery, CAF interaction, EMT, and local therapy early screening. Capan-1 is a high-priority model for BRCA2-related and DDR research. BxPC-3 is suitable for KRAS wild-type and EGFR-dependent directions. AsPC-1 is suitable for high-metastasis, liver metastasis, and peritoneal dissemination directions. This model has high standardization and good reproducibility, suitable for early screening and PK/PD research; its limitations are the inability to truly reflect pancreatic stroma, drug penetration barrier, low perfusion, immunosuppression, liver metastasis, peritoneal dissemination, and postoperative relapse.

Modeling and dosing timelines
Subcutaneous inoculation typically reaches enrollment volume within 1–4 weeks, with randomization commonly performed at tumor volumes of approximately 80–150 mm³. The conventional treatment period is 2–4 weeks. For resistance, withdrawal rechallenge, long-term continuous dosing, or sustained-release formulations, this can be extended to 4–8 weeks. Small molecules can be dosed daily or every other day; chemotherapy can be dosed cyclically; antibodies, ADCs, and bispecifics require dosing intervals based on half-life, target expression, and toxicity window.

Detection endpoints

Basic efficacy layer: TGI, RTV, terminal tumor weight, body weight, general condition, and progression-free time
Molecular and pathway layer: KRAS mutation background, pERK, pS6, EGFR, DDR-related markers, γH2AX, RAD51, target antigen expression, and pathway inhibition
Stroma and drug distribution layer: αSMA, collagen, FAP, CD31, hypoxia-related markers, drug tissue distribution, and tumor tissue exposure
PK/PD layer: Plasma drug concentration, tumor tissue concentration, target occupancy, pathway inhibition, ADC/nanoparticle tissue distribution, and exposure-efficacy relationship

Recommended positive controls
Gemcitabine at 50–100 mg/kg IP, 1–2 times weekly; nab-paclitaxel at 10–30 mg/kg IV or IP, once weekly or at intervals. Olaparib at 25–100 mg/kg oral daily for BRCA/PALB2/HRD-related models. RMC-6236 and daraxonrasib can serve as KRAS/RAS direction development references.

Pancreatic Orthotopic Model

Human pancreatic orthotopic models typically use PANC-1-luc, MiaPaCa-2-luc, AsPC-1-luc, BxPC-3-luc, or Capan-1-luc, inoculated or implanted into the pancreatic tail or body of NSG or NOD-SCID mice. Syngeneic pancreatic orthotopic models use Pan02/Panc02-luc or KPC-luc in C57BL/6 immunocompetent mice. Orthotopic burden can be tracked via BLI/IVIS, ultrasound, or terminal dissection.

Model characteristics
PANC-1-luc and MiaPaCa-2-luc are suitable for KRAS pathway, small molecules, nanodelivery, and local formulation research; BxPC-3-luc is suitable for KRAS wild-type and EGFR-dependent directions; Capan-1-luc is suitable for DDR and BRCA/PALB2 directions; AsPC-1-luc is suitable for high-metastasis, liver metastasis, and peritoneal dissemination research; Pan02/Panc02-luc and KPC-luc are suitable for immunotherapy, TME remodeling, local therapy, metastasis, and relapse research. This model is closer to the real organ environment, suitable for studying highly fibrotic stroma, local invasion, drug penetration, metastasis, and relapse; its limitations are complex surgery, lower throughput, and greater variability.

Modeling and dosing timelines
Orthotopic models typically form monitorable burden within 1–3 weeks after modeling, and luc-labeled models can be stratified for enrollment via BLI. The conventional treatment period is 2–6 weeks. If studying metastasis, relapse, local sustained release, immunotherapy, or long-term maintenance, the observation period can be extended. Treatment can begin after orthotopic BLI signal confirmation, or after orthotopic burden reaches a predetermined standard, followed by resection, local treatment, radiotherapy, or interventional combination.

Detection endpoints

Orthotopic burden layer: BLI/IVIS, ultrasound, orthotopic pancreatic tumor burden, terminal tumor weight, survival, and body weight
Pancreatic microenvironment layer: αSMA, collagen, FAP, CAF markers, CD31, low perfusion/hypoxia markers, perineural invasion, and drug tissue distribution
Metastasis and dissemination layer: Liver metastasis, peritoneal dissemination, ascites, lymph node metastasis, organ involvement, and survival
Immune layer: In syngeneic models, CD8/FoxP3, MDSC, macrophages, PD-L1, cytokines, TCR repertoire, single-cell sequencing, and spatial immune analysis can be detected

Recommended positive controls
Gemcitabine combined with nab-paclitaxel as a common chemotherapy reference for orthotopic models. FOLFIRINOX-like regimens as an intensified chemotherapy framework, requiring split design based on animal tolerance. Capan-1 orthotopic models can set platinum induction and olaparib maintenance references. Pan02/Panc02 or KPC syngeneic orthotopic models can set anti-PD-1 antibody, anti-CTLA-4 antibody, STING agonist, or cytokine strategies.

Liver Metastasis Model

Liver metastasis models can use AsPC-1, MiaPaCa-2, Pan02/Panc02, or KPC cells, established via hemi-splenic, intrasplenic, or portal vein injection for experimental liver metastasis, or by spontaneous liver metastasis from pancreatic orthotopic models.

Model characteristics
Suitable for liver colonization, liver-targeted delivery, anti-microenvironment remodeling, anti-metastasis strategies, postoperative minimal residual disease, and perioperative therapy research. Intrasplenic or portal vein models have relatively high success rates and shorter cycles, suitable for comparing liver colonization inhibition capacity; orthotopic spontaneous liver metastasis models are closer to the natural clinical course but have longer cycles and greater variability.

Detection endpoints
Liver metastatic nodule count, liver weight, BLI/IVIS, liver tissue HE, intrahepatic immune infiltration, liver tissue drug concentration, and survival.

Recommended positive controls
Gemcitabine combined with nab-paclitaxel, FOLFIRINOX-like regimens, or oxaliplatin-related regimens can serve as basic references. For immunotherapy or local delivery programs, controls should be set in syngeneic or local exposure-compatible models.

Peritoneal Dissemination Model

Peritoneal dissemination models can use AsPC-1-luc, MiaPaCa-2-luc, Pan02/Panc02-luc, or KPC-luc, established via intraperitoneal injection, or by spontaneous progression from pancreatic orthotopic models.

Model characteristics
Suitable for intraperitoneal local therapy, intraperitoneal perfusion, sustained-release devices, nanodelivery, anti-dissemination strategies, and ascites-related research. This model is suitable for peritoneal scenario evaluation, but tumor burden heterogeneity is significant, requiring standardized scoring and sampling systems.

Detection endpoints
Peritoneal nodule count, PCI-like score, ascites volume, BLI/IVIS, organ involvement, intraperitoneal drug exposure, and survival.

Recommended positive controls
Gemcitabine, nab-paclitaxel, and FOLFIRINOX-like regimens can serve as systemic therapy references. Intraperitoneal local delivery programs should set systemic dosing, intraperitoneal dosing, and blank vehicle controls.

Orthotopic Spontaneous Metastasis Model

AsPC-1-luc, MiaPaCa-2-luc, Pan02-luc, or KPC-luc pancreatic orthotopic models can be used to observe the natural process of primary lesion dissemination to the liver or peritoneum.

Model characteristics
Suitable for anti-metastasis, anti-colonization, perioperative therapy, long-term maintenance, and MRD research. This model is closer to the natural clinical course but has longer experimental cycles and greater individual variability, requiring stable orthotopic tumor formation and dynamic tracking systems.

Detection endpoints
Orthotopic burden, liver metastasis, peritoneal dissemination, ascites, survival, BLI, pathology, and metastatic lesion drug exposure.

Recommended positive controls
Gemcitabine combined with nab-paclitaxel or FOLFIRINOX-like regimens can serve as systemic therapy references; immunotherapy or local delivery programs should set compatible references based on the model system.

Syngeneic Subcutaneous Model

Pan02/Panc02 or KPC-derived cells can be inoculated subcutaneously in C57BL/6 mice to establish an early immune efficacy platform for PDAC in an intact immune system background. Randomization occurs when tumors reach approximately 50–100 mm³.

Model characteristics
Suitable for immune checkpoint, STING, cytokines, radiotherapy combination, local therapy, TME remodeling, and combination therapy early screening.

Detection endpoints
Tumor volume, TGI, body weight, survival, flow cytometry immune profiling, CD8/FoxP3, MDSC, macrophages, PD-L1, cytokines, and IHC/IF.

Recommended positive controls
Gemcitabine, nab-paclitaxel, anti-PD-1 antibody, anti-CTLA-4 antibody, STING agonists, or radiotherapy combination can serve as mechanism references. Antibody doses typically start at 100–200 μg/mouse IP, twice weekly or once every 3 days.

Syngeneic Pancreatic Orthotopic Model

Pan02/Panc02-luc or KPC-luc can establish orthotopic models in the pancreas of C57BL/6 mice. This model simultaneously retains the pancreatic organ environment and intact immune system, and is a high-priority platform for PDAC immunotherapy research.

Model characteristics
Suitable for immunotherapy, local therapy, radiotherapy combination, TME remodeling, liver metastasis, peritoneal dissemination, and postoperative relapse research. Its limitation is that biological differences remain between murine and human tumors; human target drugs, TCE, and cell therapy still require humanized model supplementary validation.

Detection endpoints
Orthotopic tumor burden, BLI/IVIS, liver metastasis, peritoneal dissemination, survival, CD8/FoxP3, MDSC, macrophages, single-cell analysis, TCR repertoire, cytokines, and spatial immune analysis.

Recommended positive controls
Anti-PD-1 antibody, anti-CTLA-4 antibody, STING agonists, or cytokine strategies can serve as immunotherapy references. Antibody doses can start at 100–200 μg/mouse IP, twice weekly or once every 3 days. Gemcitabine combined with nab-paclitaxel can serve as a chemotherapy reference.

huPBMC Combined with Human PDAC Model

The huPBMC model establishes a short-term human immune effector environment by infusing human peripheral blood mononuclear cells into immunodeficient mice, combined with PANC-1, MiaPaCa-2, BxPC-3, AsPC-1, Capan-1, and other human PDAC models.

Model characteristics
Suitable for bispecifics, TCE, CAR-T/NK, human cytokines, human immune checkpoints, and ADC programs dependent on human immune system effects. This model has high cost, long cycles, significant donor variability, and carries xGvHD or cytokine release risk.

Detection endpoints
hCD45, hCD3, hCD4, hCD8, hNK, T cell activation, tumor infiltration, IFN-γ, TNF-α, IL-6, Granzyme B, tumor burden, body weight, CRS, and xGvHD risk markers.

Recommended positive controls
anti-human PD-1 antibody, anti-human PD-L1 antibody, or anti-human CTLA-4 antibody can serve as mechanism references. TCE, CAR-T, or CAR-NK programs should include target-positive, low/negative, effector cell, and empty vector/irrelevant TCE controls. Cell therapy doses are often designed on the order of 10⁶–10⁷ cells/mouse.

huHSC Combined with Human PDAC Model

The huHSC model reconstructs a longer-term human immune system via human hematopoietic stem cells, suitable for long-cycle immunotherapy, complex combination strategies, and microenvironment mechanism research.

Model characteristics
Suitable for sustained immune activation, TCE, CAR-T/NK, ADC combination immunotherapy, immune resistance, complex TME mechanisms, and longer-cycle efficacy observation. This model has high cost, long cycles, significant donor variability, and carries xGvHD or cytokine release risk; it is not recommended as a first-round screening platform.

Detection endpoints
Human immune reconstitution ratio, T/B/NK/myeloid cell spectrum, tumor infiltration, cytokines, human immune checkpoint expression, tumor burden, survival, and major organ pathology.

Post-Resection Relapse and Minimal Residual Disease Model

This model typically uses pancreatic orthotopic models as the base, first establishing trackable orthotopic lesions, followed by primary lesion resection, debulking, or local treatment, then observing local relapse, liver metastasis recurrence, peritoneal relapse, and survival. Preoperative therapy, postoperative adjuvant therapy, perioperative combination therapy, or maintenance therapy can be set up.

Model characteristics
Suitable for perioperative therapy, postoperative relapse, minimal residual disease clearance, and long-term maintenance therapy research. This model has strong clinical mapping but is technically complex with longer cycles, requiring high consistency in orthotopic tumor formation, local resection, and long-term follow-up; it is not suitable for early large-scale screening.

Modeling and dosing timelines

First establish pancreatic orthotopic lesions and confirm burden by BLI/IVIS or ultrasound. Premature treatment may result in an insufficient relapse window, while delayed treatment may result in a high liver metastasis baseline. Primary lesion resection, debulking, or local treatment is performed according to the program; postoperative observation continues for 4–10 weeks or longer, recording local relapse, liver metastasis, peritoneal dissemination, and survival.

Detection endpoints

Relapse layer: Time to local relapse, BLI relapse, liver metastasis recurrence, peritoneal relapse, and survival
MRD layer: Residual lesion burden, ctDNA, metastatic lesion pathology, and residual markers
Mechanism layer: KRAS pathway, pERK, pS6, αSMA, collagen, CD31, immune infiltration, and target retention
Safety layer: Body weight, postoperative recovery, liver and kidney function, major organ pathology, and dosing tolerance

Recommended positive controls
Gemcitabine combined with nab-paclitaxel or FOLFIRINOX-like regimens can serve as perioperative chemotherapy references. Syngeneic relapse models can set anti-PD-1 antibody, anti-CTLA-4 antibody, or STING-related references.

How to Select the Right Model for Your Program?

By Molecular Background

By Drug Type

By Research Objective

By Route of Administration

By Development Pathway

KRAS-mutant programs: Prioritize PANC-1, MiaPaCa-2, AsPC-1, or KPC-derived cells. Use subcutaneous CDX for early screening, then escalate to orthotopic models for pancreatic microenvironment, stromal barrier, and pathway inhibition validation.
DDR/BRCA/PALB2 programs: Prioritize Capan-1 and CFPAC-1. For platinum-sensitive maintenance, PARP combination, or relapse inhibition programs, escalate to orthotopic or relapse models with DNA damage and long-term observation endpoints.
KRAS wild-type / EGFR-dependent programs: Prioritize BxPC-3. For EGFR antibody, bispecific, or ADC programs, re-confirm EGFR or target antigen expression retention.
High-metastasis programs: Prioritize AsPC-1, MiaPaCa-2, CFPAC-1, or KPC models and escalate early to liver metastasis and peritoneal dissemination models.

Cytotoxic and general chemotherapy: Gemcitabine, nab-paclitaxel, and FOLFIRINOX-like regimens can serve as general chemotherapy references. Subcutaneous models can be used for early screening; orthotopic and metastasis models are better suited to translational scenario evaluation.
PARP and DDR agents: Olaparib can serve as a gBRCA-related maintenance therapy reference. Prioritize Capan-1 and other DDR-related models; design studies with platinum induction, maintenance therapy, and time to relapse.
KRAS and downstream pathway agents: For KRAS inhibitor or RAS(ON) inhibitor programs, select models based on the specific mutation background. RMC-6236, daraxonrasib, and similar agents are better suited as frontier development references; dose and grouping should be determined based on compound properties, PK, and pilot studies.
Immunotherapy and TME remodeling: For anti-PD-1, anti-PD-L1, anti-CTLA-4, STING agonists, cytokines, and myeloid regulatory programs, prioritize Pan02/Panc02 or KPC syngeneic immunocompetent models; key validation should escalate to syngeneic orthotopic models.
Local delivery, radiotherapy, and interventional programs: For local delivery, sustained-release devices, radiotherapy, ablation, embolization, and penetration-enhancing programs, prioritize pancreatic orthotopic models. CEND-1-class penetration-enhancing strategies can serve as development references; focus on drug tissue distribution and orthotopic penetration.
TCE, CAR-T/NK, and human immune-dependent therapies: For TCE, CAR-T/NK, human cytokines, and antibodies or ADCs highly dependent on human immune effects, select target-positive human PDAC models and escalate to huPBMC or huHSC humanized platforms.

Rapid tumor shrinkage and PK/PD: Prioritize subcutaneous CDX. Key endpoints include TGI, RTV, terminal tumor weight, body weight, plasma drug concentration, tumor tissue concentration, and target pathway changes.
Pancreatic orthotopic microenvironment and drug penetration: Prioritize pancreatic orthotopic models. Key endpoints include orthotopic burden, αSMA, collagen, CD31, drug tissue distribution, liver metastasis, peritoneal dissemination, and survival.
Liver metastasis: Consider intrasplenic, hemi-splenic, or portal vein injection liver metastasis models, or orthotopic spontaneous liver metastasis models. Key endpoints include liver metastatic nodule count, liver weight, imaging signal, liver histopathology, and survival.
Peritoneal dissemination: Prioritize intraperitoneal dissemination models. Key endpoints include peritoneal nodule count, PCI-like score, ascites volume, intraperitoneal drug exposure, and survival.
Postoperative relapse and MRD clearance: Prioritize pancreatic orthotopic models with post-resection relapse observation. Key endpoints include local relapse, liver metastasis recurrence, peritoneal relapse, BLI, survival, and residual disease burden.
Immune microenvironment remodeling: Prioritize syngeneic immunocompetent orthotopic models. Key endpoints include CD8/FoxP3, MDSC, macrophages, cytokines, TCR repertoire, single-cell analysis, and spatial immune analysis.

Systemic administration: Oral, intraperitoneal, intravenous, and subcutaneous dosing are suitable for subcutaneous CDX, orthotopic, metastasis, and immune models. Set dosing frequency based on half-life, toxicity window, and model progression rate.
Intraperitoneal administration: Suitable for peritoneal dissemination, ascites, local high-exposure formulations, nanodelivery, and intraperitoneal immune activation. Evaluate intraperitoneal drug exposure, peritoneal nodules, ascites, and local safety.
Local pancreatic administration: Local injection, local sustained release, postoperative cavity dosing, and peripancreatic delivery are better suited to pancreatic orthotopic or relapse models. Focus on orthotopic tissue concentration, local toxicity, and peripancreatic tissue response.
Radiotherapy and interventional combination: For radiotherapy, ablation, embolization, and interventional combination programs, define local treatment window, dosing sequence, and sampling time. Orthotopic models should serve as the primary decision platform.
Combination immunotherapy dosing: Set dosing sequence based on mechanism, such as modulating stroma or myeloid suppressive environment first followed by immune checkpoint combination, or radiotherapy/chemotherapy-induced immunogenic changes followed by immunotherapy.

KRAS pathway, small molecule, and ADC pathway: PANC-1/MiaPaCa-2/BxPC-3 subcutaneous CDX early screening → pancreatic orthotopic model validation of organ relevance → liver metastasis or peritoneal dissemination model for deeper evaluation.
DDR, BRCA, and PALB2 pathway: Capan-1/CFPAC-1 subcutaneous model early screening → pancreatic orthotopic model validation → post-resection relapse or liver metastasis model for deeper evaluation.
Immunotherapy and TME pathway: Pan02/Panc02 or KPC syngeneic subcutaneous early screening → syngeneic orthotopic model key validation → liver metastasis, peritoneal dissemination, or relapse models when needed.
Local delivery and radiotherapy/interventional pathway: Pancreatic orthotopic model as the primary platform → local drug distribution and safety validation → peritoneal dissemination, liver metastasis, or postoperative relapse models when needed.

Why Alfa Cytology?

Stromal Architecture & Kras-Driven Modeling

Pancreatic cancer is characterized by dense desmoplastic stroma and ubiquitous KRAS mutations. Alfa Cytology designs tailored evaluation pathways incorporating fibrotic microenvironments and specific driver backgrounds (KRAS G12D/G12V, TP53, SMAD4, CDKN2A) to reflect real-world therapeutic barriers.

Stratified Cell Line & Syngeneic Directory

Model choice directly influences drug perfusion and immune infiltration readouts. Alfa Cytology helps clients match appropriate systems—such as PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, KPC series, and PAN02—based on driver status, extracellular matrix density, and immunocompetence.

Orthotopic Pancreatic & Liver Metastasis Models

Flank subcutaneous models fail to mimic high interstitial fluid pressure, dense stroma, or hepatic tropism. Alfa Cytology helps clients generate high-fidelity translational evidence using orthotopic pancreatic head/body implantation and portal vein liver metastasis models.

Target Validation & Integrated PK/PD Workflows

Programs targeting mutant KRAS, TME stroma-modifying agents, ADC targets, or combination immunotherapies require deep tissue penetration analysis. Alfa Cytology configures stromal biomarker scoring, intratumoral drug delivery metrics, and integrated PK/PD workflows.

Alfa Cytology is a global leader in PDAC translational research, delivering integrated animal model solutions that span KRAS-driven biology, stromal barrier, drug penetration, liver metastasis, peritoneal dissemination, and immune microenvironment evaluation. If you are interested in our services, please don't hesitate to contact us to learn how we can accelerate your PDAC drug development.

Reference

Akhuba L, et al. Where Do We Stand with Immunotherapy for Advanced Pancreatic Ductal Adenocarcinoma: A Synopsis of Clinical Outcomes. Biomedicines. 2022;10(12):3196.

For research use only.

Solutions

Online Inquiry

Name *

Email *

Phone *

Services Interested *

Project Description

Please note that we are not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.