Date:June 21, 2016
Ovarian cancer is considered a relatively rare gynecologic malignancy but has one of the highest mortality rates due to the non-specific symptoms that occur in early stage disease. This results in most women being diagnosed with advanced stage disease. The incidence of ovarian cancer within the United States is approximately 22,000 cases per year and results in approximately 14,000 deaths per year. Despite the advances being made within cancer as a whole, overall survival rates for women diagnosed with ovarian cancer have not dramatically improved in decades and it remains an area of highly unmet medical need.
Ovarian cancer is categorized into multiple subtypes depending on their histopathology, molecularsignatures, and disease outcomes, with the most common subtype being high-grade serous carcinoma. Preclinical work in ovarian cancer remains an active area of pursuit in biotech and pharma companies. At MI Bioresearch, we aim to provide models with the most relevance to our clients. To accomplish this, we have one murine syngeneic ovarian cancer cell line and eight human ovarian cancer cell lines (see Table 1). Six of our nine ovarian cancer cell lines express luciferase, which allows us to track and monitor disease longitudinally with bioluminescence imaging (BLI). Having both the parental lines and the luciferase expressing lines allows us to test agents in a variety of tissue sites. To this end, we have utilized many of our lines as standard subcutaneous models (see Figures 1A, 1B, and 1C) for rapid evaluation in early PK/PD studies or screening of anti-tumor activity.
Growth of ovarian cancer cell lines in the subcutaneous space:
Fig. 1A: SK-OV-3 in nu/nu mice.
Fig. 1C: IGROV-1 in nu/nu mice.
Fig. 1B: SK-OV-3 treated with cisplatin or docetaxel.
As many patients with ovarian cancer develop peritoneal ascites, one standard preclinical method is to deliver these cell lines intraperitoneally (IP) to mimic this disease state. With our luciferase expressing lines we are able to track and monitor disease establishment and progression with BLI and report out quantitative measurements of tumor burden and therapeutic response of test materials. Both the SK-OV-3 (Fig 2A, B) and OVCAR-3 (Fig 2C, D) models have been characterized in this setting. The SK-OV-3-luc model has about a five-day tumor doubling time and a median overall survival of approximately 60 days. The OVCAR-3-luc model grows more quickly in vivo and shows a 1.5 day tumor doubling time and median overall survival time of about 24 days.
Growth of ovarian cancer cell lines in the peritoneal space:
Fig. 2A: SK-OV-3 in SCID beige mice.
Fig. 2B: SK-OV-3 in SCID beige mice.
Fig. 2C: OVCAR-3 in C.B-17 SCID mice.
Fig. 2D: OVCAR-3 in C.B-17 SCID mice.
While intraperitoneal injection of tumor cells mimics an orthotopic setting, this is not truly an orthotopic model of solid tumor disease. Thus, a number of years ago we capitalized on our very skilled technical staff and developed a true orthotopic model by direct injection into the bursa of the mouse ovary. Once again, the use of BLI allows us to longitudinally monitor disease and provide highly quantitative data sets to support assessment of novel therapies (see Figure 3).
Growth of the OVCAR-3 ovarian cancer cell line following intra-bursa implantation in SCID beige mice:
Fig. 3A: Representative BLI images over time.
Fig. 3B: Quantification of BLI signal over time.
At MI Bioresearch, we have developed ovarian cancer models to enable rapid screening of novel compounds in the SC setting, but our commitment to modeling cancer in the appropriate microenvironment led us to develop orthotopic models that leverage our imaging expertise. Our in vivo data from the SC, IP, and intra-bursa settings allows us to provide highly relevant preclinical models that will be worthwhile for those investigators pursuing approaches to develop drugs for ovarian cancer.
For more information or to speak to us about your next ovarian cancer study, contact us today. We would love to help you with your upcoming oncology projects.