Oncology

Clinical Background 

Cancer is a serious public health concern with well over one million new diagnoses annually in the US alone. Cancer kills one in four Americans, and is second only to cardiovascular disease as the most common cause of death. Treatment for most cancers is insufficient despite early detection methods. As a result, there is an urgent need for novel anti-cancer agents. Biomodels contributes to the drug development process by providing a cost-effective outsourcing opportunity enabling companies to rapidly identify lead compounds for testing in humans.

 

As members of the American Association for Cancer Research (AACR), our Oncology Group has presented their own work at AACR-sponsored conferences. Our uniquely personal approach to our clients’ needs recognizes that the goals of different companies of various sizes and in different stages are not the same.

 

Preclinical Models

Model Description Length Endpoints
Xenograft Tumor cells are implanted subcutaneously in rats or mice Variable Tumor volume, histology, cytokine induction, protein, and RNA expression.
Orthotopic Cells are implanted directly into the desired organ site in rats or mice
Syngeneic Cells are from the same species as  host and are immunocompatible therefore immunocompetent animals can be used.
Cancer Stem Cells Tumor initiating cells are enriched from a heterogeneous bulk tumor cell population.  Cancer stem cells are studied in comparison to the “parent” line and can be assessed in 3-D culture in vitro or implanted into animals in vivo.  In vitro: Tumorsphere Formation, Proliferation, Survival, Migration, FACS profile.
In Vivo: Tumor volume, metastasis, histology, cytokine induction, protein and RNA Expression
In Vitro Assays Assays for: Proliferation and survival, migration and invasion, tumorspheres/colony formation, and FACS biomarker analysis Tumor cell growth, invasiveness and survival
* Several models are compatible with IVIS imaging for in-life monitoring of disease progression.

 

*All commercial cell lines are available, examples include:

Indication Cell Line Available Models
Breast Carcinoma MDA-MB-231,MDA-MB-468, 4T1 Xenograft, Orthotopic, Syngeneic, In Vitro Assays, Cancer Stem Cells
Colorectal Carcinoma HCT-15, HCT-116, HT-29, CT26 Xenograft, Orthotopic, In Vitro Assays, Cancer Stem Cells
Pancreatic Carcinoma AsPC-1, PANC-1, MIA PaCa-2 Xenograft, Orthotopic,In Vitro Assays, Cancer Stem Cells
Head and Neck Carcinoma FaDu Xenograft, Orthotopic, In Vitro Assays, Cancer Stem Cells
Lung Carcinoma A549, NIH-H460, NCI-H69 (small cell), NCI-H82 (small cell), NIH-H520, Lewis Lung Xenograft, Orthotopic, In Vitro Assays, Cancer Stem Cells
Glioma Carcinoma U87-MG, U118-MG, F98 Xenograft, Orthotopic, Syngeneic, In Vitro Assays, Cancer Stem Cells
Additional cell lines available:
Areolar (L-929)
Bladder (RT-4)
Cancer (Walker 256)
Leukemia Pro-monocytic (HL-60)
Leukemia ATL ( Molt-4, K562, CEM)
Leukemia T-cell (Kasumi-1, Jurkat)
Lymphoma (RAMOS)
Lymphoma-Mantle Cell (JeKo, Z138)
Lymphoma T-cell (EL-4)
Liver (HepG2, Hep 3B, Prt-plc-5)
Multiple Myeloma (RPMI 8226)
Melanoma(SK-MEL-28, A375, B16-FO, B16-F1O)
Ovarian Carcinoma (A2780, OVCAR-3, SK-OV-3)
Prostate (Du145, LNCaP, PC-3)
Renal (Caki-1, Caki-2, A498, HEK-293)
Rhabdomyosarcoma (A-673)
Stomach (NCI-N87)
Tongue (CAL-27)
Thyroid Carcinoma (TT)

 

In Vitro Assays

In our primary screening program, compounds can be quickly tested for their ability to inhibit tumor growth and invasive migration in cultured cells. We can also examine the impact of test compounds on tumorspheres/colony formation. We are equipped with cell separation and FACS for further analysis of cell populations and drug response.

• Growth/Proliferation
• Survival/TUNEL
• Migration
• Tumorsphere formation
• Cell separation
• FACS analysis
• RNA/Protein analysis

 

Xenografts

Subcutaneous injection of tumor cells in mice and rats offers a relatively simple and efficient tumor model system to test the efficacy of potential therapeutics for the treatment of cancer. Furthermore, the model is useful in addressing the presence of drug-related toxicity. We offer a wide variety of traditional tumor cell lines which can be studied as xenografts in both mice and rats. Experimental endpoints for xenograft studies include: tumor volume, histology, cytokine induction, protein, and RNA expression.

 

Orthotopic

Sub-cutaneous xenograft models of cancer can be useful for evaluating the potential of a novel therapeutic compound, however there is significant evidence to suggest that the behavior of tumor cells can be significantly different when grown as a sub-cutaneous xenograft, compared to their behavior when implanted into either the tissue of origin, or implanted into a different organ, simulating a metastatic tumor. Orthotopic models tend to be more clinically relevant and better predictors of drug efficacy. Additionally, tumor cells implanted directly into in their tissue of origin tend to grow better. As the interest for orthotopic models for anti-cancer drug screening have significantly increased in recent years, Biomodels has met that need with the ongoing development of several orthotopic models. Specifically, models of glioblastoma, lymphoma, breast, colorectal, lung, head and neck cancer.

 

Syngeneic

Syngeneic models provide the advantage of studying the interaction between the immune system and the tumor because the cells are from the same species as the host. Immunocompetent animals are used in this model and cells can be directly implanted into the tissue site for a highly clinically relevant analysis. Tumor growth in syngeneic model is rapid and provides highly translatable endpoints including tumor growth, metastasis, tumor-infiltrating lymphocyte characterizations, histology, and a variety of biomarker analyses.

 

Cancer Stem Cells

Evidence for the presence of tumor initiating cells (cancer stem cell) is rapidly increasing. This cell population is thought to be resistant to many standards of care agents and responsible for patient relapse.  Because there are established cell surface markers to identify cancer stem cells, they can be isolated from established heterogeneous “parent” cell lines and studied as an enriched population in vitro 3-D culture assays or they can be implanted into animals and studied in vivo. This provides a way to test therapeutics that specifically targets this sub population of cells in comparison to the heterogeneous parent cell line.