Ovarian Cancer

• OVCAR3: one of the classic and widely used ovarian cancer models, suitable for platinum, taxane, PARP combination, FRα-related research, and HGSOC direction early screening.
• OVCAR4: more suitable for TP53, HRD, PARP inhibition, and HGSOC stratification research; FRα direction can also consider OVCAR4.
• OVCAR5: can serve as an HGSOC-related model supplement, suitable for basic efficacy, mechanism research, and stratification validation.
• Kuramochi: often regarded as one of the human models closer to HGSOC molecular characteristics, suitable for mechanism research, HRD/PARP, molecular stratification, and translational validation.
• OVSAHO: suitable for HGSOC stratification, TP53/HRD-related mechanisms, and PARP direction research.
• Caov3: can serve as an HGSOC-related model and general efficacy supplementary platform.

• A2780: suitable for platinum-sensitive, standard therapy efficacy, and early dose exploration.
• A2780cis: commonly used for cisplatin resistance research, suitable for platinum resistance, resistance reversal, post-relapse therapy, and combination strategy validation.
• OVCAR8: with strong peritoneal dissemination and metastasis potential, suitable for peritoneal dissemination, relapse, maintenance therapy, and anti-peritoneal lesion research; OVCAR8-luc is suitable for IVIS dynamic monitoring.
• HeyA8: suitable for high-invasion, peritoneal dissemination, metastasis, and relapse-related research; HeyA8-luc can serve as a key model.
• SKOV3: fast-growing, suitable for HER2, FRα, ADC, local intraperitoneal administration, and high-proliferation scenarios.
• ES2: strong invasiveness, suitable for rapid dissemination, high-malignancy phenotype, peritoneal metastasis, and high-invasion efficacy screening.

• ID8: a commonly used base platform in ovarian cancer immunocompetent research, capable of forming peritoneal lesions and ascites in a C57BL/6 background, suitable for immunotherapy, TME, and peritoneal microenvironment research.
• ID8-luc: suitable for IVIS dynamic monitoring of peritoneal dissemination, orthotopic burden, peritoneal relapse, and maintenance therapy efficacy.
• ID8-VEGF: more suitable for ascites formation, angiogenesis, immunosuppression, and anti-VEGF combination immunotherapy research.
• ID8-Trp53-/- and high-metastasis sublines: can enhance HGSOC clinical relevance or peritoneal dissemination speed, suitable for mid-to-late stage efficacy, immune microenvironment, relapse, and maintenance therapy research.

• FRα programs should prioritize cell lines with stable FRα expression that is not easily lost in vivo, such as OVCAR3, OVCAR4, and under certain conditions IGROV1 or SKOV3 models.
• PARP inhibitors, DNA damage repair, and HRD directions should prioritize models with clearer BRCA/HRD background, and distinguish platinum-sensitive, post-platinum maintenance, and platinum-resistant levels.
• ADC programs, especially FRα, TROP2, NaPi2b directions, should simultaneously focus on antigen expression homogeneity, in vivo stability, peritoneal lesion accessibility, and drug tissue distribution.

Subcutaneous CDX models typically involve inoculating human ovarian 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.

• HGSOC subcutaneous CDX: OVCAR3, OVCAR4, OVSAHO, Kuramochi, Caov3
• Platinum-resistant and high-invasion subcutaneous CDX: A2780cis, OVCAR8, HeyA8, SKOV3, ES2
• FRα and ADC direction subcutaneous CDX: OVCAR3, OVCAR4, SKOV3, IGROV1, or FRα-positive lines

Model characteristics
HGSOC subcutaneous CDX is suitable for early screening of small molecules, cytotoxic agents, PARP inhibitors, ADCs, and basic targeted agents. Platinum-resistant and high-invasion subcutaneous CDX is suitable for platinum resistance, ADC, combination strategies, high invasion, and relapse direction early screening. FRα, TROP2, NaPi2b, or other ADC programs should first confirm target expression, then select target-positive models for subcutaneous efficacy screening. This model has high standardization and good reproducibility, suitable for early screening and PK/PD research; its limitations are the inability to reflect peritoneal dissemination, omental metastasis, ascites formation, and maintenance therapy pathways.

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 maintenance therapy, PARP combination, resistance research, or ADC interval dosing, this can be extended to 4–8 weeks. Small molecules can be dosed daily or every other day; carboplatin, cisplatin, and paclitaxel can be dosed cyclically; ADCs and antibody drugs require interval dosing based on half-life, target expression, and toxicity window.

Detection endpoints

• Basic efficacy layer: TGI, RTV, terminal tumor weight, body weight, general condition, progression-free time, and survival
• HGSOC and DDR layer: FRα, γH2AX, RAD51, BRCA/HRD-related markers, TP53 background, DNA damage, and apoptosis
• Mechanism layer: Ki67, cleaved caspase-3, TUNEL, CD31, target expression, resistance markers, and target pathway inhibition
• PK/PD layer: Plasma drug concentration, tumor tissue concentration, target occupancy, pathway inhibition, ADC tissue distribution, and exposure-efficacy relationship

Recommended positive controls
Carboplatin at 30–60 mg/kg IP or IV, once weekly or cyclically; cisplatin at 2–5 mg/kg IP or IV; paclitaxel at 10–20 mg/kg IP or IV, once weekly for 2–4 consecutive weeks. Pegylated liposomal doxorubicin at 2–5 mg/kg IV, weekly or at intervals. Olaparib at 25–100 mg/kg oral once or twice daily; niraparib at 25–50 mg/kg oral once daily. Mirvetuximab soravtansine as a clinical mapping reference for FRα-positive, platinum-resistant direction.

Human orthotopic models typically use OVCAR8-luc, HeyA8-luc, SKOV3-luc, ES2-luc, and other cells, inoculated under the ovarian capsule or into local ovarian tissue of immunodeficient mice, with IVIS tracking of orthotopic burden and peritoneal spread. ID8-luc, ID8-VEGF, and ID8 high-metastasis derivatives can establish syngeneic orthotopic models in C57BL/6 mice.

Model characteristics
OVCAR8-luc, HeyA8-luc, and ES2-luc more readily form invasion and peritoneal dissemination; SKOV3-luc is more suitable for ADC, targeted agent, and local delivery research; ID8-luc is more suitable for orthotopic and dissemination research in an immunocompetent background. This model is closer to the organ environment, but has complex surgery, lower throughput, and greater inter-batch variability, with strong dependence on luc labeling and in vivo imaging.

Modeling and dosing timelines
Orthotopic models typically form monitorable burden within 1–3 weeks after modeling, and IVIS confirmation of enrollment is recommended. The conventional treatment period is 2–6 weeks. If studying omental metastasis, ascites, relapse, or maintenance therapy, the observation period can be extended. Treatment can begin after orthotopic BLI signal confirmation. If studying relapse or maintenance therapy, remission confirmation after induction therapy should be set before entering maintenance observation.

Detection endpoints

• Orthotopic burden layer: Orthotopic BLI signal, ovarian local tumor burden, tumor weight, local invasion, tissue pathology, and survival
• Peritoneal spread layer: Omental metastasis, peritoneal nodule count, peritoneal lesions, ascites volume, IVIS, and PCI-like score
• Mechanism layer: FRα, Ki67, cleaved caspase-3, γH2AX, RAD51, CD31, F4/80, and target expression
• Immune layer: In syngeneic models, CD8, Treg, MDSC, macrophages, ascites immune cells, and cytokines can be detected

Recommended positive controls
Carboplatin combined with paclitaxel as a first-line scenario reference. Olaparib or niraparib can be used for post-platinum maintenance therapy pathway. Bevacizumab or anti-VEGF-related strategies as anti-angiogenesis and ascites-related research references.

Human peritoneal dissemination models are typically established via intraperitoneal injection of luc-labeled ovarian cancer cells. Commonly used cells include OVCAR8-luc, HeyA8-luc, SKOV3-luc, ES2-luc, and OVCAR3-luc, with NSG or NOD-SCID mice as hosts.

Model characteristics
OVCAR8-luc, HeyA8-luc, and ES2-luc disseminate rapidly, suitable for rapid efficacy validation; OVCAR3-luc is more suitable for HGSOC background and longer-term treatment design; SKOV3-luc is more suitable for ADC and local intraperitoneal delivery directions. Peritoneal dissemination models are one of the most translationally valuable ovarian cancer models, capable of reflecting peritoneal implantation, omental metastasis, and ascites formation; their limitations are complex quantification and greater inter-batch variability.

Detection endpoints
Total peritoneal BLI signal, peritoneal nodule count, omental weight, ascites volume, total peritoneal lesion burden, PCI-like score, survival, pathology, and target expression.

Recommended positive controls
Carboplatin combined with paclitaxel as a first-line or general scenario reference. Platinum-resistant scenarios can set liposomal doxorubicin or other later-line references. FRα-positive peritoneal dissemination models can set mirvetuximab soravtansine-related references.

Immunocompetent peritoneal dissemination models typically use ID8, ID8-luc, ID8-VEGF, or high-metastasis ID8 sublines inoculated intraperitoneally in C57BL/6 mice, forming peritoneal nodules, omental lesions, and ascites.

Model characteristics
Suitable for immunotherapy, ascites microenvironment, myeloid suppression, T cell exhaustion, local peritoneal immunity, and relapse maintenance therapy research. Syngeneic models can evaluate the intact immune system and peritoneal microenvironment, and are the core platform for ovarian cancer immunotherapy programs. Their limitation is the difference between murine tumors and human target expression; human ADCs, bispecifics, and cell therapy still require CDX or humanized model supplementary validation.

Detection endpoints
Peritoneal lesion burden, ascites volume, ascites cytology, CD8/Treg, myeloid cell profile, F4/80, cytokines, tumor tissue immune infiltration, and survival.

Recommended positive controls
anti-PD-1 or anti-PD-L1 can be administered IP at 100–200 μg/mouse, twice weekly or once every 3 days, for 2–3 consecutive weeks as a starting reference. Anti-VEGF-related strategies can be designed in combination with PD-1/PD-L1, PARP, or chemotherapy. PARP inhibitor combined with immune checkpoint can be used to explore the relationship between DNA damage and immune microenvironment.

Omental metastasis models can use OVCAR8-HM, ES2-HM, and ID8 high-metastasis sublines. High-metastasis sublines are typically obtained through in vivo selection, with stronger omental colonization capacity and peritoneal dissemination tendency.

Model characteristics
Suitable for studying omental tropism, early adhesion, mesothelial cell interaction, ECM remodeling, and anti-metastasis strategies. Omental metastasis models are more suitable for site-specific colonization and anti-adhesion mechanism research and should not replace all peritoneal dissemination models.

Detection endpoints
Omental nodule burden, omental weight, peritoneal dissemination extent, tissue pathology, EMT, ECM-related markers, and survival.

Recommended positive controls
Carboplatin combined with paclitaxel as a basic reference. FRα-positive programs can set mirvetuximab soravtansine-related references. Anti-VEGF-related strategies can serve as anti-angiogenesis and omental metastasis direction references.

Liver colonization models can use intrasplenic or portal vein injection, commonly with ES2, SKOV3, OVCAR8-derived high-invasion lines. This model is suitable for advanced distant metastasis and post-circulation liver colonization questions.

Model characteristics
Liver colonization models are typically supplementary platforms in ovarian cancer and should not replace peritoneal dissemination models as the primary decision basis.

Detection endpoints
Liver metastatic nodule count, liver weight, BLI/IVIS, liver tissue HE, intrahepatic drug concentration, Ki67, apoptosis, and survival.

Recommended positive controls
Carboplatin combined with paclitaxel can serve as a systemic therapy reference. For ADC or targeted agent programs, target-positive models should be selected and liver metastatic lesion target expression verified.

Lung colonization models can be established via tail vein injection of high-invasion ovarian cancer cells, suitable for evaluating post-circulation lung colonization and anti-distant metastasis capacity.

Model characteristics
Lung colonization models can answer distant colonization questions, but the more common and core translational scenarios in ovarian cancer remain peritoneal dissemination, omental metastasis, and ascites.

Detection endpoints
Lung nodule count, lung weight, BLI, lung tissue pathology, metastatic area, and survival.

Recommended positive controls
Carboplatin combined with paclitaxel can serve as a systemic therapy reference. For ADC or targeted agent programs, target-positive models should be selected and lung metastatic lesion target expression verified.

ID8 or ID8-derived lines can be inoculated subcutaneously in C57BL/6 mice to establish an early immune efficacy platform in an intact immune system background.

Model characteristics
Suitable for immune checkpoint, STING, innate immune agonists, cytokines, PARP combination immunotherapy, and combination therapy early screening. Syngeneic subcutaneous models are suitable for immune early screening, but if hits are not escalated to peritoneal dissemination or orthotopic models, it is typically difficult to fully cover the ovarian cancer peritoneal immune microenvironment.

Detection endpoints
Tumor volume, TGI, survival, body weight, flow cytometry immune profiling, IHC, spatial immune analysis, CD8/Treg, myeloid cell profile, and cytokines.

Recommended positive controls
anti-PD-1 or anti-PD-L1 can be administered IP at 100–200 μg/mouse, twice weekly or once every 3 days, for 2–3 consecutive weeks as a starting reference. Anti-VEGF-related strategies can be designed in combination with PD-1/PD-L1, PARP, or chemotherapy.

ID8-luc, ID8-VEGF, and high-metastasis ID8 sublines can be used for orthotopic or peritoneal dissemination models in C57BL/6 mice. This model can form peritoneal nodules, omental lesions, and ascites.

Model characteristics
Suitable for immunotherapy, ascites immunology, myeloid suppression, T cell exhaustion, relapse maintenance therapy, anti-angiogenesis combination immunotherapy, and local peritoneal therapy research. This model can evaluate the intact immune system and peritoneal microenvironment, and is the core platform for ovarian cancer immunotherapy programs. Its limitation is the difference between murine tumors and human target expression; human ADCs, bispecifics, and cell therapy still require CDX or humanized model supplementary validation.

Detection endpoints
Peritoneal lesion burden, ascites, ascites cytology, CD8/Treg, MDSC, macrophages, F4/80, PD-L1, cytokines, TCR repertoire, and survival.

Recommended positive controls
Anti-PD-1 or anti-PD-L1 can be administered IP at 100–200 μg/mouse, twice weekly or once every 3 days, for 2–3 consecutive weeks as a starting reference. Anti-VEGF-related strategies can be designed in combination with PD-1/PD-L1, PARP, or chemotherapy. PARP inhibitor combined with immune checkpoint can be used to explore the relationship between DNA damage and immune microenvironment.

The huPBMC model establishes a short-term human immune effector environment by infusing human peripheral blood mononuclear cells into immunodeficient mice, combined with human ovarian cancer cell lines. Commonly used cells include OVCAR3, OVCAR4, OVCAR8, SKOV3, HeyA8, and ES2.

Model characteristics
Suitable for FRα/CD3 bispecifics, TCE, CAR-T/NK, human cytokines, human immune checkpoints, and ADC or bispecific programs highly dependent on human immune effects. This model has long cycles, high cost, significant donor variability, and carries xGVHD or cytokine release risk; it is not recommended as the highest-throughput early screening.

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, anti-human PD-L1, or other human target antibodies 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.

The huHSC model reconstructs a longer-term human immune system via human hematopoietic stem cells, suitable for complex immune mechanisms, sustained immunotherapy, and immune resistance research.

Model characteristics
Suitable for long-cycle human immunotherapy, TCE, CAR-T/NK, bispecifics, immune combination, peritoneal microenvironment, and sustained efficacy observation. This model has long cycles, high cost, 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, or other human target antibodies 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.

Relapse, maintenance therapy, and resistance models typically use orthotopic or peritoneal dissemination models as the base, first inducing lesion reduction with carboplatin/paclitaxel, then entering PARP inhibitor, anti-angiogenic agent, ADC, or combination regimen maintenance observation. Commonly used models include OVCAR8-luc, HeyA8-luc, ID8-luc, A2780cis, and SKOV3-luc.

Model characteristics
Suitable for relapse inhibition, MRD clearance, maintenance therapy, post-platinum-resistance therapy, and long-term survival research. This model is closer to the clinical pathway but has long cycles and complex design, and is not suitable for first-round rapid screening.

Detection endpoints
Initial remission, time to relapse, peritoneal relapse, ascites, survival, MRD-related markers, FRα retention, γH2AX, RAD51, and immune microenvironment changes.

Recommended positive controls
Olaparib or niraparib can serve as PARP maintenance therapy references, recommended after platinum-induced remission. FRα-positive relapse models can set mirvetuximab soravtansine-related references. Syngeneic ID8 relapse models can set anti-PD-1, anti-PD-L1, or anti-VEGF combination references.