Prostate cancer is a malignancy with distinct disease stages and significant AR pathway dependence, and is one of the most common malignancies among men worldwide. Alfa Cytology is a global leader in cancer research. With our extensive experience and advanced platforms, our talented scientists provide one-stop solutions for prostate cancer animal model development, efficacy evaluation, orthotopic prostate model validation, bone metastasis and lung metastasis evaluation, castration relapse studies, tumor immunology testing, target expression validation, pathology testing, molecular mechanism testing, and PK/PD, based on client candidate drugs, disease stage, AR dependence status, PSA/PSMA expression, metastatic organs, castration background, immune system requirements, and R&D stages. We also provides 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 Prostate Cancer
Prostate cancer is a malignant tumor originating from prostate epithelium and is one of the most common malignancies among men worldwide. Prostate cancer is characterized by distinct disease stages and significant AR pathway dependence, with marked differences in castration-sensitive, castration-resistant, AR variant, and neuroendocrine transformation settings.Clinically, prostate cancer is commonly managed based on disease stage and AR dependence status. Castration-sensitive prostate cancer is mainly treated with ADT, AR pathway inhibitors, and androgen synthesis inhibitors; castration-resistant prostate cancer (CRPC) relies more on later-line AR pathway therapy, AR degraders, PARP inhibitors, PSMA radioligands, and chemotherapy. AR-V7, AR amplification, and neuroendocrine transformation are key issues in CRPC resistance research. Common metastatic organs in prostate cancer include bone, lymph nodes, lung, and liver. Among these, bone metastasis is a high-priority scenario in translational research and requires dedicated modeling in drug evaluation. The prostate cancer immune microenvironment, tumor-infiltrating lymphocytes, myeloid cells, and cytokine networks play important roles in treatment response and resistance.
Fig. 1 Overview of genetic alterations in prostate cancer. (He Y, et al.; 2022)
Therefore, prostate cancer animal studies need to be differentially designed based on disease stage, AR dependence status, PSMA expression, metastatic organs, castration background, 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 prostate cancer animal experimental research, built around castration-sensitive prostate cancer, castration-resistant prostate cancer, persistent AR activation, AR-V7/AR variant, bone metastasis, PSMA radioligand, PSMA/CD3 bispecifics, humanized immunotherapy, and castration relapse/MRD scenarios. Leveraging this integrated platform, we provide end-to-end services covering the full prostate cancer drug development workflow.
Preclinical Efficacy Studies
Prostate cancer drug development requires model selection based on castration-sensitive vs castration-resistant stage, AR dependence, AR-V7/AR variant status, PSMA expression, bone metastasis, PSMA radioligand therapy, PSMA/CD3 bispecifics, humanized immunotherapy, and castration relapse/MRD scenarios. Alfa Cytology provides integrated animal study solutions, from cell line selection to model validation, for AR pathway inhibitors, androgen synthesis inhibitors, AR degraders/PROTACs, PARP inhibitors, PSMA radioligands, ADCs, bispecifics, TCEs, CAR-T/NK, PD-1/PD-L1, STING, radiotherapy combination, and castration relapse programs.
Clinical Relevance Studies
When programs advance to orthotopic prostate microenvironment, bone metastasis, lung metastasis, castration relapse, PSMA radioligand therapy, PSMA/CD3 bispecific therapy, immunotherapy, humanized immunotherapy, or postoperative relapse/MRD stages, Alfa Cytology can further configure orthotopic prostate models, bone metastasis models, experimental lung metastasis/systemic dissemination models, syngeneic immunocompetent models (RM-1/TRAMP-C2/Myc-CaP), humanized immune models, or castration relapse models to help clients generate evidence more aligned with clinical scenarios.
Prostate Cancer Mechanism Research
For prostate cancer studies, experimental design typically needs to address disease stage, AR dependence, AR variant status, PSMA expression, bone microenvironment, castration background, and immune microenvironment simultaneously. Alfa Cytology provides model development, dosing intervention, pathology testing, immunology testing, protein testing, and RNA testing services, covering AR pathway, AR-V7, AR amplification, PSA, PSMA, HRR/PARP, bone metastasis, castration relapse, and MRD clearance.
In Vitro and In Vivo Layered Validation
Animal studies can address whether a candidate inhibits tumor growth, local invasion, bone destruction, lung metastasis, or castration relapse; zebrafish platforms provide high-throughput in vivo screening covering tumor proliferation, prostate orthotopic colonization, local invasion, bone/lung metastatic invasion, angiogenesis, immune co-culture, and drug toxicity; cell-based experiments validate proliferation, apoptosis, migration and invasion, AR/AR-V7, PSA, PSMA, DNA damage repair, drug internalization, and immune killing.
Candidate Screening
Early screening typically requires rapid assessment of whether a candidate demonstrates in vivo antitumor signals. Alfa Cytology conducts TGI, RTV, PK/PD, PSA, AR, AR-V7, PSMA, and target evaluations using 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, AR, AR-V7, PSA, PSMA, γH2AX, RAD51, PD-L1, CD8/Treg, myeloid cell profiling, cytokines, bone tissue exposure, PET/molecular imaging, and human immune reconstitution 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
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R&D Project
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Cell Lines
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Host System
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Preferred Model
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Key Endpoints
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| Early efficacy screening and dose exploration |
LNCaP, VCaP, 22Rv1, C4-2, C4-2B, DU145, PC-3, PC-3M |
BALB/c nude, NOD-SCID, NSG mice |
Subcutaneous CDX |
TGI, RTV, terminal tumor weight, body weight, PSA, AR, PSMA, Ki67, PK/PD. |
| Castration-sensitive / AR-dependent programs |
LNCaP, VCaP |
BALB/c nude, NSG mice |
AR-dependent subcutaneous CDX, with castration or escalation to orthotopic model when needed |
PSA, AR, PSMA, TGI, castration response, androgen regulation, PK/PD. |
| AR pathway inhibitors / androgen synthesis inhibitors |
LNCaP, VCaP |
BALB/c nude, NSG or NOD-SCID mice |
LNCaP / VCaP subcutaneous CDX, orthotopic model for confirmation |
PSA decline, AR expression, TGI, pathway inhibition, regrowth after withdrawal. |
| Castration-resistant / persistent AR activation |
22Rv1, C4-2, C4-2B |
BALB/c nude, NSG mice |
CRPC subcutaneous CDX, with castration background or escalation to orthotopic model |
AR-V7, AR amplification, PSA, TGI, resistance-related pathways, survival. |
| AR degrader / PROTAC programs |
22Rv1, C4-2, C4-2B |
BALB/c nude, NSG mice |
22Rv1, C4-2, C4-2B subcutaneous CDX, with orthotopic or bone metastasis confirmation when needed |
AR degradation, AR-V7, PSA, pathway recovery, RTV, PK/PD. |
| AR-low / AR-independent invasive programs |
DU145, PC-3, PC-3M |
BALB/c nude, NOD-SCID, NSG mice |
High-invasion CDX, metastasis model for confirmation |
TGI, invasion and metastasis markers, EMT, lung/bone colonization, drug exposure. |
| Orthotopic prostate microenvironment and local invasion |
LNCaP-luc, VCaP-luc, C4-2B-luc; RM-1, TRAMP-C2, Myc-CaP |
NSG or NOD-SCID mice; C57BL/6, FVB or matched immunocompetent mice |
Orthotopic prostate model |
Orthotopic burden, BLI, PSA, local invasion, lymph node metastasis, survival. |
| Bone metastasis / bone pain / bone destruction |
C4-2B, VCaP, PC-3M; RM-1, Myc-CaP |
BALB/c nude, NSG mice; C57BL/6, FVB or matched immunocompetent mice |
Left ventricle injection or tibial/femoral inoculation model |
micro-CT, X-ray, bone destruction score, pain behavior, survival, bone remodeling markers. |
| PSMA radioligand / PSMA PET / bone metastasis scenario |
LNCaP, VCaP, C4-2B and other PSMA-positive models |
BALB/c nude, NSG or NOD-SCID mice |
PSMA-positive subcutaneous CDX, orthotopic or bone metastasis model |
PSMA expression, PET/molecular imaging requirement, bone lesion burden, tissue exposure, survival. |
| PSMA/CD3 bispecific / TCE programs |
VCaP, LNCaP, 22Rv1, C4-2B and other PSMA-positive models |
huPBMC or huHSC-reconstituted NSG/NOG mice |
PSMA-positive CDX for target confirmation, humanized model for human immune effect validation |
PSMA expression, hCD45, hCD3, hCD8, cytokines, T cell activation, CRS/xGvHD risk. |
| HRR deficiency / PARP combination |
Human prostate cancer models with clear HRR/BRCA status, 22Rv1, C4-2, C4-2B and others |
BALB/c nude, NSG mice |
Molecular background-matched CDX, with CRPC or bone metastasis model when needed |
DNA damage, PARP pathway, γH2AX, RAD51, TGI, combination effect. |
| Immunotherapy / TME remodeling |
RM-1, TRAMP-C2, Myc-CaP |
C57BL/6, FVB or matched immunocompetent mice |
Syngeneic immunocompetent subcutaneous screening, orthotopic model for validation |
CD8/Treg, MDSC, macrophages, cytokines, TCR repertoire, orthotopic burden. |
| Castration relapse / postoperative relapse / MRD clearance |
RM-1, Myc-CaP; C4-2B-luc, VCaP-luc, LNCaP-luc |
C57BL/6, FVB or matched immunocompetent mice; NSG or NOD-SCID mice |
Orthotopic model with castration, withdrawal, resection, or relapse observation |
Post-castration relapse, BLI, PSA re-elevation, local relapse, distant metastasis, survival. |
Comprehensive Test and Data Analysis Platform
For prostate cancer programs focused on castration-sensitive/castration-resistant stratification, AR/AR-V7 pathway, and bone metastasis evaluation, we configure TGI, RTV, terminal tumor weight, BLI, orthotopic tumor burden, PSA, AR, AR-V7, PSMA, Ki67, cleaved caspase-3, DNA damage markers, micro-CT, bone destruction score, bone pain behavior, survival, bone remodeling markers, immune infiltration, flow cytometry, cytokines, PET/molecular imaging requirement, and bone tissue exposure, forming an integrated data chain linking AR pathway, bone microenvironment, and immune microenvironment.
Multimodal In Vivo Imaging
- IVIS Spectrum photon bioluminescence quantification for prostate orthotopic tumors and bone metastasis tracking
- 7.0T small-animal high-field MRI for orthotopic prostate lesion and bone metastasis scanning
- micro-CT 3D reconstruction for bone destruction, bone mineral density, and bone metastasis assessment
Pathology and IHC/IF Staining
- AR / AR-V7 / PSMA / PSA target and pathway assessment
- Ki67 / Cleaved-Caspase 3 / γH2AX proliferation, apoptosis, and DNA damage index
- mIF multiplex immunofluorescence for in situ target and prostate TME quantification
TME Microenvironment and Immune Profiling
- Prostate tumor TILs (CD4+ / CD8+ / Treg) and MDSC analysis
- Post-castration immune microenvironment change analysis
- Cytokine storm (IFN-γ / IL-6) CBA suspension array
Access Our Prostate Cancer Model Library
Prostate Cancer Cell Line Panel
Alfa Cytology's prostate cancer cell line panel covers five key areas,including disease stage, AR dependence status, AR-V7/AR variant, PSMA expression, and immuno-oncology, enabling cell line selection and matching based on disease stage, AR status, PSMA expression, and immune system requirements.
Castration-Sensitive and AR-Dependent-Related Cell Lines
- LNCaP: a classic AR-dependent model suitable for AR inhibitors, androgen synthesis inhibitors, PSA readout, endocrine therapy response, and early targeted agent screening.
- VCaP: with higher AR expression level, commonly used for TMPRSS2-ERG-related background and PSMA-related program research.
Castration-Resistant and Persistent AR Activation-Related Cell Lines
- 22Rv1: commonly used for AR splice variant, especially AR-V7-related resistance research, suitable for AR degraders, AR-V7 pathway, later-line AR strategies, and PROTAC research.
- C4-2: a castration-resistant model derived from LNCaP evolution, suitable for studying persistent AR activation, castration background growth, and transformed CRPC.
- C4-2B: further exhibits stronger bone tropism, suitable for castration resistance and bone metastasis coupling research.
AR-Low and High-Invasion-Related Cell Lines
- DU145: suitable for AR-low, invasion, resistance, and local therapy research.
- PC-3: one of the commonly used invasion and metastasis models, suitable for AR-independent, high-invasion, migration, metastasis mechanisms, local delivery, and cytotoxic drug screening.
- PC-3M: a high-metastasis derivative, more suitable for lung, bone and other organ colonization and high-invasion metastasis research.
Immuno-Oncology-Related Cell Lines
- RM-1: fast-growing, suitable for immune checkpoint, STING, cytokines, local therapy, and combination therapy early screening.
- TRAMP-C2: more suitable for prostate orthotopic and local microenvironment research, also suitable for immunotherapy, local therapy, and radiotherapy combination.
- Myc-CaP: suitable for AR-related, castration response, and immunocompetent research in FVB background.
PSMA and Target-Related Cell Lines
- PSMA: LNCaP, VCaP, C4-2B and other models with stable PSMA expression.
- PSMA radioligand: bone metastasis and molecular imaging requirements should be prioritized.
- PSMA/CD3 bispecifics or TCE: should enter humanized immune models to validate human immune effects.
Bone Metastasis-Related Cell Lines
- C4-2B, VCaP, PC-3M, RM-1, Myc-CaP: suitable for left ventricle injection or tibial/femoral inoculation models.
Prostate Cancer Animal Model Panel
Alfa Cytology provides end-to-end prostate cancer 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 castration-sensitive prostate cancer, castration-resistant prostate cancer, persistent AR activation, AR-V7/AR variant, bone metastasis, PSMA radioligand, PSMA/CD3 bispecifics, humanized immunotherapy, and castration relapse/MRD research. Each model can be customized to match your program's disease stage, AR dependence status, PSA/PSMA expression, metastatic organs, castration background, immune system requirements, and R&D stage, from early screening to clinical relevance validation.
Subcutaneous Xenograft Model (CDX)
Subcutaneous CDX typically involves inoculating human prostate cancer 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.
- AR-dependent subcutaneous CDX: LNCaP, VCaP
- Castration-resistant subcutaneous CDX: 22Rv1, C4-2, C4-2B
- AR-low or high-invasion subcutaneous CDX: DU145, PC-3, PC-3M
Model characteristics
LNCaP and VCaP are suitable for AR pathway inhibitors, androgen synthesis inhibitors, AR degraders, PSA readout, and PSMA-related programs. 22Rv1, C4-2, and C4-2B are suitable for CRPC, AR-V7, persistent AR activation, AR degraders, PROTAC, and later-line therapy research. DU145, PC-3, and PC-3M are suitable for invasion, migration, cytotoxic agents, partial ADCs, local delivery, and metastasis program early screening; these models are not suitable as the core evaluation platform for classical AR pathway drugs. This model has high standardization and reproducibility, suitable for early screening and PK/PD research; its limitations are that it cannot fully reflect prostate local microenvironment, castration relapse, bone metastasis, and real immune background.
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 withdrawal rechallenge, castration resistance establishment, long-term AR suppression, or PSMA-related slow-acting therapy, this can be extended to 4–8 weeks or longer. AR-dependent programs can be designed with surgical castration, medical castration, androgen supplementation, or post-castration relapse according to research objectives, and the castration timing should be clarified at the protocol stage.
Detection endpoints
- Basic efficacy layer: TGI, RTV, terminal tumor weight, body weight, general condition, and progression-free time
- AR/PSA mechanism layer: PSA, AR, AR-V7, PSMA, TMPRSS2-ERG-related background, AR downstream pathways, and post-withdrawal pathway recovery
- Proliferation and apoptosis layer: Ki67, cleaved caspase-3, TUNEL, necrosis, and cell cycle markers
- PK/PD layer: Plasma drug concentration, tumor tissue concentration, target occupancy, pathway inhibition, PSMA expression retention, and exposure-efficacy relationship
Recommended positive controls
Enzalutamide at 10–30 mg/kg oral daily dosing; abiraterone at 50–200 mg/kg oral daily dosing. Docetaxel at 5–10 mg/kg IV or IP, once weekly or cyclically; cabazitaxel as later-line reference. PARP combination programs set olaparib, talazoparib, or niraparib based on HRR/BRCA status. PSMA direction can reference lutetium-177 PSMA radioligand or JANX007-class strategies.
Orthotopic Prostate Model
Human orthotopic models typically use LNCaP-luc, VCaP-luc, or C4-2B-luc inoculated intraprostatically in immunodeficient mice, with BLI/IVIS tracking of orthotopic tumor burden. RM-1, TRAMP-C2, and Myc-CaP can establish syngeneic orthotopic prostate models in matched strains.
Model characteristics
LNCaP and VCaP orthotopic models are more suitable for AR-dependent and local therapy evaluation; C4-2B orthotopic models are more suitable for castration resistance and bone metastasis trend research; RM-1 orthotopic models grow fast, suitable for immunotherapy and local therapy early screening; TRAMP-C2 and Myc-CaP are more suitable for organ microenvironment and AR/castration-related research. This model is closer to the prostate organ environment, suitable for local invasion, relapse, and minimal residual disease research. Its limitations are complex procedures, low throughput, and strong dependence on luc labeling or high-quality imaging platforms.
Modeling and dosing timelines
Orthotopic models typically form monitorable burden within 1–3 weeks after modeling, depending on cell line, inoculation amount, and host background. Luc-labeled models can confirm enrollment via BLI. The conventional treatment period is 2–6 weeks. If studying castration relapse, postoperative relapse, or long-term AR suppression, observation can be extended. Surgical or medical castration can be performed after orthotopic tumor establishment to observe BLI decline, PSA decline, and subsequent relapse.
Detection endpoints
- Orthotopic burden layer: BLI/IVIS, orthotopic tumor burden, prostate local pathology, survival, and local invasion
- AR mechanism layer: PSA, AR, AR-V7, PSMA, androgen-related pathways, and post-castration relapse
- Metastasis layer: Lymph node metastasis, lung metastasis, bone metastasis trend, and distant tissue pathology
- Immune layer: In syngeneic models, CD8, Treg, MDSC, macrophages, cytokines, TCR repertoire, and single-cell/spatial immune analysis
Recommended positive controls
Enzalutamide and abiraterone can serve as AR pathway references, distinguishing simple castration, ARPI treatment, and combination regimens. Docetaxel as CRPC or local therapy reference; cabazitaxel as later-line reference. Local radiotherapy or local delivery designed by equipment conditions and animal tolerance. Syngeneic orthotopic models can set anti-PD-1 antibody, anti-PD-L1 antibody, STING agonists, or cytokine strategies.
Bone metastasis models can use left ventricle injection, intratibial injection, or intrafemoral injection. Left ventricle injection is more suitable for simulating bone colonization after systemic dissemination; intratibial or intrafemoral injection is more suitable for studying bone microenvironment, bone destruction, bone pain, and local therapy. Commonly used models include C4-2B, VCaP, PC-3M, RM-1, and Myc-CaP.
Model characteristics
C4-2B is suitable for CRPC and bone metastasis coupling research; VCaP is suitable for PSMA and AR-related bone lesions; PC-3M is suitable for high-invasion and bone colonization; RM-1 and Myc-CaP are suitable for bone-related research in immunocompetent background. Left ventricle models are more suitable for studying bone colonization and organ tropism; intratibial models are more suitable for bone microenvironment and local bone therapy; the two cannot substitute for each other.
Detection endpoints
micro-CT, X-ray, bone destruction score, bone density, bone remodeling markers, pain or lameness behavior, survival, bone tissue pathology, PSMA expression, bone tissue drug exposure, and PET/molecular imaging requirements.
Recommended positive controls
Docetaxel, enzalutamide, or abiraterone as basic references based on AR status; anti-bone resorption drugs for bone destruction research; PSMA direction can reference lutetium-177 PSMA radioligand, with radioactive experiments requiring separate condition confirmation.
Experimental Lung Metastasis and Systemic Dissemination Model
Tail vein injection can establish lung colonization models, and left ventricle injection can be used for systemic dissemination and bone/multi-organ colonization. Commonly used cells include PC-3M, DU145, and RM-1.
Model characteristics
Suitable for post-circulation colonization, organ tropism, high-invasion phenotype, and anti-metastasis drug early screening. This model has shorter cycles and focused endpoints, but does not fully represent the complete natural process from orthotopic prostate tumor to distant metastasis. If closer clinical course is desired, escalation to orthotopic spontaneous metastasis or relapse models is required.
Detection endpoints
Lung nodule count, lung weight, BLI/IVIS, tissue pathology, distant organ burden, survival, and metastasis-related markers.
Recommended positive controls
Docetaxel, cabazitaxel, or AR pathway drugs set based on model AR status; RM-1 models can set anti-PD-1/PD-L1 or STING references.
Syngeneic Subcutaneous Model
RM-1, TRAMP-C2, and Myc-CaP can establish subcutaneous models in matched strains, retaining an intact immune system. This model is suitable for immune checkpoint, STING, cytokines, radiotherapy combination, and TME early screening.
Model characteristics
RM-1 is suitable for rapid immune screening and combination therapy; TRAMP-C2 is suitable for prostate cancer organ background extension research; Myc-CaP is suitable for AR-related and castration response research.
Detection endpoints
Tumor volume, TGI, survival, body weight, flow cytometry immune profiling, CD8/Treg, MDSC, macrophages, cytokines, IHC, and spatial immune analysis.
Recommended positive controls
anti-PD-1, anti-PD-L1 antibodies at 100–200 μg/mouse IP, twice weekly or once every 3 days, for 2–3 consecutive weeks. STING agonists, cytokines, or radiotherapy combinations set according to mechanism.
Syngeneic Orthotopic Model
RM-1, TRAMP-C2, and Myc-CaP can be inoculated intraprostatically in matched strains to establish syngeneic orthotopic models. This model simultaneously retains organ microenvironment and intact immune system.
Model characteristics
Suitable for immunotherapy, local therapy, radiotherapy combination, castration relapse, minimal residual disease, and local metastasis research. In prostate cancer immunotherapy or local therapy programs, syngeneic orthotopic models typically have greater translational value than syngeneic subcutaneous models. Its limitation is that murine tumors differ from human tumors, and human PSMA, AR, or bispecific drugs still require CDX or humanized model supplementary validation.
Detection endpoints
Orthotopic tumor burden, survival, local invasion, distant metastasis, immune infiltration, flow cytometry, single-cell sequencing, TCR repertoire, cytokines, and spatial immune analysis.
Recommended positive controls
anti-PD-1, anti-PD-L1 antibodies at 100–200 μg/mouse IP, twice weekly or once every 3 days. STING agonists, cytokines, radiotherapy combinations, or local therapy set according to mechanism.
huPBMC Combined with Human Prostate Cancer Model
The huPBMC model establishes a short-term human immune effector environment by infusing human peripheral blood mononuclear cells into immunodeficient mice, combined with human prostate cancer models. Recommended cells include VCaP, 22Rv1, C4-2B, LNCaP, and PC-3, selected based on PSMA or target antigen expression.
Model characteristics
Suitable for PSMA/CD3 bispecifics, TCE, CAR-T/NK, human cytokines, human immune checkpoints, and ADCs or bispecifics highly dependent on human immune 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
JANX007-class PSMA/CD3 strategies as TCE reference, with PSMA-positive, low/negative, effector cell, and irrelevant TCE controls. PSMA CAR-T/NK programs should include target-positive and low-expression models. anti-human PD-1/PD-L1 antibodies set by model window.
huHSC Combined with Human Prostate Cancer Model
The huHSC model reconstructs a relatively long-term human immune system via human hematopoietic stem cells, suitable for long-cycle human immune reconstitution, complex combination regimens, and microenvironment mechanism research.
Model characteristics
Suitable for sustained immune activation, resistance evolution, PSMA bispecifics, CAR-T/NK, immune combination therapy, and complex TME mechanism research. 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.
Recommended positive controls
anti-human PD-1, anti-human PD-L1 antibodies set by model window; PSMA/CD3 or CAR-T/NK programs set target-positive, low-expression, and effector cell controls.
Castration relapse models can be established based on LNCaP, VCaP, C4-2, C4-2B, or Myc-CaP models. First, tumor burden is formed, then surgical or medical castration is performed, and the initial decline followed by regrowth is observed.
Model characteristics
Suitable for castration-sensitive to castration-resistant transition, persistent AR pathway activation, AR-V7, AR amplification, withdrawal rechallenge, and long-term AR suppression research.
Detection endpoints
BLI/IVIS, PSA decline and re-elevation, tumor regrowth, AR, AR-V7, PSMA, Ki67, apoptosis, pathway recovery, and survival.
Recommended positive controls
Enzalutamide and abiraterone as AR pathway references. AR degrader or PROTAC programs can reference ARV-766-class frontier strategies.
Postoperative Relapse and Minimal Residual Disease Model
The model can observe relapse after primary lesion resection, debulking, or local therapy based on orthotopic prostate models. Luc-labeled cells help track minimal residual disease.
Model characteristics
Suitable for postoperative adjuvant therapy, post-local-therapy relapse, minimal residual disease clearance, post-castration relapse, and distant dissemination research.
Detection endpoints
BLI relapse, local relapse, lymph node metastasis, bone/lung metastasis, survival, PSA, AR pathway recovery, PSMA retention, and immune microenvironment changes.
Recommended positive controls
Docetaxel as later-line chemotherapy reference; cabazitaxel for even later-line research. PARP combination programs set talazoparib/enzalutamide, olaparib/abiraterone, or niraparib/abiraterone based on HRR/BRCA status. PSMA direction can reference lutetium-177 PSMA radioligand.
Model characteristics
AR drug resistance can use 22Rv1, C4-2, C4-2B, or long-term dosing-induced resistant models to evaluate AR degraders, PROTAC, later-line AR strategies, and combination therapy. Chemotherapy resistance can use docetaxel-resistant derivatives or DU145/PC-3 invasive models. PARP resistance and HRR background programs should set models based on BRCA/ATM gene status.
Detection endpoints
AR, AR-V7, PSA, PSMA, DNA damage markers, γH2AX, RAD51, pathway recovery, regrowth curves, and survival.
Recommended positive controls
Enzalutamide and abiraterone set by AR status; docetaxel and cabazitaxel for chemotherapy resistance; PARP combination programs set by HRR/BRCA background.
How to Select the Right Model for Your Program？
By Disease Stage
By Drug Type
By Research Objective
By Route of Administration
By Development Pathway
- Castration-sensitive programs: Prioritize LNCaP or VCaP. Start with subcutaneous CDX; escalate to orthotopic models when local organ microenvironment or long-term castration response is involved.
- Castration-resistant programs: Prioritize 22Rv1, C4-2, and C4-2B. Add castration background or withdrawal rechallenge designs when needed.
- AR-independent and high-invasion programs: Prioritize DU145, PC-3, and PC-3M. Suitable for cytotoxic agents, metastasis mechanisms, local delivery, and selected ADC programs.
- Advanced bone metastasis programs: Prioritize bone metastasis models. Subcutaneous models serve only as early efficacy signals.
- AR pathway agents: Select AR-dependent or CRPC models. Endpoints should cover PSA, AR, AR-V7, and AR pathway inhibition.
- Chemotherapy and later-line agents: Consider 22Rv1, C4-2, DU145, PC-3, or PC-3M. Escalate to bone metastasis models for metastasis or bone lesion programs.
- PARP and HRR-deficient agents: Confirm HRR/BRCA status and set up studies based on genetic background and tolerability.
- PSMA radioligands: Confirm PSMA expression first; prioritize orthotopic or bone metastasis models. Separately confirm radiation safety and compliance requirements.
- PSMA/CD3 bispecifics, TCEs, and cell therapy: Select PSMA-positive human models and escalate to huPBMC or huHSC humanized models for human immune effect validation.
- Immunotherapy and local therapy: Prioritize RM-1, TRAMP-C2, or Myc-CaP syngeneic models. Orthotopic syngeneic models are better suited to local therapy and relapse research.
- Rapid tumor shrinkage and PK/PD: Subcutaneous CDX; endpoints include TGI, RTV, terminal tumor weight, plasma drug concentration, tumor tissue concentration, PSA, and target pathway changes.
- Prostate organ microenvironment and local invasion: Orthotopic prostate models; endpoints include orthotopic burden, BLI, local invasion, lymph node metastasis, PSA, and survival.
- Bone metastasis and bone pain: Bone metastasis models; endpoints include micro-CT, X-ray, bone destruction score, pain or lameness behavior, survival, and bone remodeling markers.
- Castration relapse and MRD clearance: Orthotopic models with castration, withdrawal, resection, or long-term follow-up; endpoints include post-castration relapse, PSA re-elevation, BLI relapse, survival, and distant dissemination.
- Immune microenvironment: Syngeneic immunocompetent models; endpoints include CD8/Treg, MDSC, macrophages, cytokines, single-cell analysis, TCR repertoire, and spatial immune analysis.
- Human immune-dependent mechanisms: Humanized immune models; endpoints include human immune reconstitution, human T cell activation, tumor infiltration, cytokines, CRS/xGvHD risk, and tumor burden.
- Systemic administration: Oral, intraperitoneal, intravenous, and subcutaneous dosing are suitable for subcutaneous CDX, orthotopic, metastasis, and immune models.
- Castration combination dosing: Clarify the sequence of dosing relative to surgical castration, medical castration, or androgen restoration.
- Bone metastasis local treatment: Combine systemic therapy, local radiotherapy, anti-bone resorption, or bone-targeted delivery; evaluate bone destruction, bone pain, and bone tissue exposure.
- Radioligand and molecular imaging: Separately confirm radiopharmaceutical management, molecular imaging, dosing, safety, and waste handling requirements.
- Cell therapy dosing: Set dosing timing based on tumor burden, PSMA expression, human immune reconstitution, and safety window.
- AR-dependent programs: LNCaP or VCaP subcutaneous CDX early screening → orthotopic model validation → castration or withdrawal rechallenge for deeper evaluation.
- CRPC and resistance programs: 22Rv1 / C4-2 / C4-2B subcutaneous CDX → orthotopic model with castration background → bone metastasis model validation.
- PSMA programs: PSMA-positive CDX target confirmation → orthotopic or bone metastasis model validation → humanized model for human immune effect confirmation.
- Immunotherapy: Syngeneic subcutaneous early screening → syngeneic orthotopic validation → relapse or bone metastasis model when needed.
Why Alfa Cytology?
Androgen Receptor & Lineage Plasticity Modeling
Prostate cancer progression is heavily governed by AR signaling and neuroendocrine differentiation. Alfa Cytology designs tailored model pathways addressing hormone-sensitive, castration-resistant (CRPC), and neuroendocrine prostate cancer (NEPC) states, avoiding cross-subtype misinterpretation.
Stratified Cell Line & PDX Directory
Model selection dictates translational relevance for anti-androgen and radionuclide therapies. Alfa Cytology helps clients match robust systems—such as LNCaP, C4-2, 22Rv1, PC-3, and Du145—based on AR expression status, PTEN/TP53 mutation, and metastatic capacity.
Orthotopic Bone & Metastasis Models
Prostate cancer exhibits a strong tropism for bone. Subcutaneous models are inadequate for studying osteoblastic/osteolytic bone lesions. Alfa Cytology helps clients generate clinical-correlative evidence through orthotopic intra-prostatic and intra-tibial/intracardiac bone metastasis models.
Target Validation & Integrated PK/PD Workflows
Programs targeting PSMA, AR-V7, PARP, or targeted radioligand therapies require precise target validation. Alfa Cytology configures PSMA expression screening, longitudinal PSA tracking, and integrated PK/PD workflows to evaluate systemic and targeted radio-immunotherapy efficacy.
Alfa Cytology is a global leader in prostate cancer translational research, delivering integrated animal model solutions that span castration-sensitive and castration-resistant disease, AR/AR-V7 pathway, bone metastasis, PSMA-targeted therapy, 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 prostate cancer drug development.
Reference
- He Y, et al. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal Transduct Target Ther. 2022;7(1):198.
For research use only.
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