Orthotopic Tumor Models

High-fidelity in vivo systems that mirror native tumor microenvironments for more predictive oncology decisions.

Orthotopic tumor models place cancer cells in their native tissue, preserving microenvironment, vasculature, and metastatic routes. Compared with subcutaneous approaches, an orthotropic model yields predictive pharmacodynamics, invasion, and spread.

Our mouse orthotopic models enable relevant imaging endpoints, immune interactions, and therapeutic response profiling, improving translational confidence for oncology programs.

Orthotopic success hinges on surgical proficiency

Orthotopic tumor models depend on precise implantation into the target tissue, procedures that directly influence take rates, metastasis patterns, and study reproducibility. Melior’s accumulated surgical skill enables reliable establishment of orthotopic xenograft and mouse orthotopic models across a deep catalog of tissues and tumor types.

Syngeneic orthotopic models preserve immunity

Syngeneic orthotopic tumor models pair murine tumors with immunocompetent hosts, preserving full immune signaling and native organ cues. They’re well-suited for checkpoint/cytokine studies, tumor–immune interaction readouts, and organotropism/metastasis assessments with longitudinal imaging.

Tissue Model (link) Typical timeline What it’s good for?
Bone K7M2 ~4 weeks Intratibial mouse orthotopic model; native microenvironment; spontaneous lung metastasis; antimetastatic efficacy & imaging endpoints.
Breast EMT6 ~3–4 weeks Mammary fat pad orthotopic tumor growth; immune-competent setting; invasion/metastasis; checkpoint and cytokine pathway studies.
Colon CT26 ~4–6 weeks Cecal wall orthotopic implantation; liver/lung organotropism; immunotherapy and chemo evaluation; longitudinal BLI-friendly.
Liver Hepa 1-6 ~8–10 weeks Intrahepatic HCC model; immuno-oncology & metastasis studies; more clinically relevant than subcutaneous.
Melanoma B16F10 ~3–4 weeks Intradermal growth in skin layer; tumor–immune interactions; immunotherapy response profiling and spatial endpoints.

Orthotopic xenograft models test human tumors

Orthotopic xenograft models place human tumor cells into the organ of origin, enabling evaluation of delivery barriers and invasive phenotypes that subcutaneous screens miss. They are ideal for testing human-tumor pharmacology and metastatic behavior with sensitive imaging and organ-specific endpoints.

Tissue Model (link) Typical timeline What it’s good for?
Brain U87 ~4-8 weeks Stereotactic brain implantation; BBB penetration, invasive growth; survival, MRI/US, BLI endpoints.
Brain LN229-Luc-Luc ~10–12 weeks Orthotopic GBM model; invasion/drug-resistance biology; therapy testing with sensitive luciferase readouts.
Breast MCF-7 ~8–10 weeks ER+ mammary fat pad orthotopic xenograft model; hormone responsiveness; endocrine therapy evaluation.
Colon HCT-15-Luc2 ~4–6 weeks Orthotopic colon implantation; liver/lung metastasis; tumor–host interaction and novel therapy assessment.
Kidney 786-O ~8–10 weeks ccRCC physiology (VHL/HIF-2α features); growth/metastasis in native site; treatment-response profiling.
Liver HepG2-Luc ~8–10 weeks Intrahepatic or spleen-to-liver seeding; realistic HCC microenvironment; growth/metastasis studies.
Ovary SK-OV-3 ~4–8 weeks Ovarian bursa injection; peritoneal spread/ascites; intraperitoneal therapy strategies and imaging.
Pancreas PANC-1-Luc2 ~8–10 weeks Parenchymal/tail implantation; desmoplasia, local invasion; delivery-limited efficacy (stromal barriers).
Prostate LNCaP-Luc2 ~8–10 weeks Androgen-dependent prostate cancer; growth/metastasis in situ; response to targeted/cytotoxic agents.

Enhance your study findings with custom services and tools

Get more from your orthotopic tumor models with tailored add-ons, including IVIS imaging and whole blood, spleen, and lymph node analyses, supported by expert surgical implantation and study design.

  • We chose Melior Discovery because they were responsive and cost effective.  We are staying with them as a chosen scientific partner because of their thoughtful scientific input to experimental design and attention to detail.  Their expertise and flexibility allowed us to quickly adapt the study design and evaluate additional outcome measures to pursue unexpected activity.

    Sridharan Rajamani, Ph.D., Senior Research Scientist

    Gilead Sciences
  • I have been working with Melior on a number of projects over the course of a few years now.  They have been a great partner throughout this time.  The scientists whom I have worked with have been great problem-solvers and were customer focused.

    Jay Lichter

    Avalon Ventures
  • Melior provided State-of-the-art Preclinical Pharmacology Support for a period of nearly a year where a series of in vivo studies were completed on a weekly basis. The staff was extremely user-friendly and the operational processes were excellent. I can recommend Melior without reservation.

    Richard DiMarchi, PhD

    Cox Professor of Chemistry & Gill Chair in Biomolecular Sciences Indiana University, Department of Chemistry
  • Because Melior could do the orthotopic intracranial implants, we were able to do survival studies with brain tumor-bearing animals that were treated with our therapy, showing a beautiful survival with our agent versus control. Talk about something that gets your investors going! These beautiful survival curves with our agent versus control and visual photos are in all of our investor decks because… it's powerful.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Melior works in many therapeutic areas, like CNS, inflammatory disease, GI, cardiovascular, and oncology. I was very pleased that when it came to doing tumor studies, both subcutaneous and intracranial, they did them well. They reported on the studies on time and did the data analysis really well.

    Bruce Ruggeri, Ph.D.

    Modifi Bio
  • Their areas of expertise are extensive, and they are very experienced, responsive, and flexible in terms of how the study is run. Their pricing is reasonable, making them the best option for a young, not well-funded company like ours.

    Maxine Gowen

    Tamuro Bio
  • Melior’s team was very experienced and knowledgeable. They were always very open to suggestions and questions, spending a lot of time helping us feel comfortable with the study design. I would give them very high marks.

    Maxine Gowen

    Tamuro Bio
  • The most important factors in choosing to work with Melior were the fit between the tests they could run and our needs, as well as their tight budget and proximity. Melior was the best fit for our research goals.

    Ira Spector

    SFA Therapeutics

IVIS bioluminescence confirms in vivo growth of orthotopic HepG2 liver tumors at week 4. The HepG2 orthotopic liver tumor model was generated by inoculating 1 × 106 HepG2 cells into the left liver lobe of nude mice through laparotomy under isoflurane anesthesia. IVIS-BLI was performed at week 4 (A). The mice were euthanized at week 8 weeks and the liver were excised (B)  and formalin fixed (C). Red circle indicated HepG2 tumor.

Immune Checkpoint Inhibitor and Chemotherapy Validation in Melanoma B16F10 orthotopic Tumor Model. 0.5 x106 B16F10 mouse melanoma cells were intradermally injected into the rear flank of C57B6 mice. Once the tumor size reached 50~100mm3, mice were randomized into groups and treated with vehicle anti-PD-1 antibody (12.5 mg/kg IP), or paclitaxel (20 mg/kg IP). Tumor volume was monitored twice per week using calipers. Both anti-PD1 antibody and paclitaxel significantly depressed tumor growth ( Arrows indicate date of treatment; both p<0.001; Data are mean ± SEM; n=5 for each group).

Get the data you need with with expert implementation on tight timelines

Expert surgical implantation across organs

Accelerated 3–10-week study timelines

Custom orthotopic designs for your study

Publications

Haddad, A. F., Young, J. S., Amara, D., Berger, M. S., Raleigh, D. R., Aghi, M. K., & Butowski, N. A. (2021). Mouse models of glioblastoma for the evaluation of novel therapeutic strategies. Neuro-Oncology Advances, 3(1), vdab100. https://doi.org/10.1093/noajnl/vdab100

Kocatürk, B., & Versteeg, H. H. (2015). Orthotopic injection of breast cancer cells into the mammary fat pad of mice to study tumor growth. Journal of Visualized Experiments, (96), e51967. https://doi.org/10.3791/51967

Terracina, K. P., Aoyagi, T., Huang, W.-C., Nagahashi, M., Yamada, A., Aoki, K., & Takabe, K. (2015). Development of a metastatic murine colon cancer model. Journal of Surgical Research, 199(1), 106–114. https://doi.org/10.1016/j.jss.2015.04.030

Hiraga, T., Nishida, D., & Horibe, K. (2024). Primary tumor-induced immunity suppresses bone metastases of breast cancer in syngeneic immunocompetent mouse models. Bone, 178, 116944. https://doi.org/10.1016/j.bone.2023.116944

Khanna, C., Prehn, J., Yeung, C., Caylor, J., Tsokos, M., & Helman, L. (2000). An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. Clinical & Experimental Metastasis, 18(3), 261–271. https://doi.org/10.1023/A:1006767007547

Frequently Asked Questions

How do I choose between syngeneic and orthotopic xenograft models?

Use syngeneic when immune pathways are central (e.g., checkpoint/cytokine work in EMT6 or CT26). These models retain intact immunity and support immunotherapy evaluation.

Choose orthotopic xenografts for human tumor biology, receptor-driven questions (e.g., ER+ MCF7), or organ barriers (e.g., BBB in U87 GBM).

Which models offer LUC2 for tracking?

Several xenograft models are available with stable Luc2 expression for noninvasive bioluminescence imaging, including:

  • LN229-Luc2 
  • MCF7-Luc2
  • HCT-15-Luc2 
  • HepG2-Luc2
  • PANC-1-Luc2
  • LNCaP-Luc2
Can we design studies that prioritize metastasis endpoints rather than primary volume?

Yes. We run orthotopic implantations with serial IVIS/BLI, histology, and survival endpoints, enabling both growth and spontaneous metastasis readouts in the same cohorts.