The Translational Oncology Research Laboratory (TORL) of the UCLA Jonsson Comprehensive Cancer Center now has the greatest collection of cervical cancer cell lines in the United States and very likely the world. This unparalleled asset was made possible by the many supporters of the Debi & Gary Fournier Cervical Cancer Research Fund.
Progress achieved to-date thanks to the Fournier Fund:
- Secured 34 cervical cancer cell lines from countries including Japan, Korea, Germany, England and the United States. Of these:
- Fourteen cell lines are fully established in the lab (uniqueness authenticated by “fingerprinting” and checked to be clean of any possible contamination).
- An additional 20 cervical cancer cell lines have been identified and are in the process of being fully established.
- The 34 cervical cancer cell lines represent the full spectrum of cervical cancer heterogeneity that is seen in the real world in patients diagnosed with cervical cancer. They include histologic subtypes that are of squamous origin, of adenocarcinoma origin and of a mixed adenosquamous origin. The cell lines also include HPV infected and non-infected cervical cancer.
- The research team has screened 67 new anti-cancer compounds against the existing cervical cancer cell line panel of 14 cell lines. Among the 67 screened anti-cancer compounds, we already have identified some interesting leads on novel drugs (e.g., bromodomain inhibitors and CDK inhibitors) that have shown high preclinical activity that would not otherwise have been identified as potentially effective drugs against cervical cancer. It is of great importance that all drugs also are tested against TORL’s breast, lung, colon, head and neck, ovarian, endometrial, prostate, pancreas and upper gastrointestinal cancer cell lines, as well as those for lymphoma, sarcoma and melanoma. The access TORL provides to more than 500 fully characterized cancer cell lines offers a unique opportunity to efficiently compare a drug’s activity across many different tumor types, while allowing us to strategically allocate the funds raised through the Debi & Gary Fournier Cervical Cancer Research Fund.
- In instances where screening of the 67 anti-cancer compounds has shown a lack of activity in the cervical cancer cell lines, this information has given us the opportunity to make early decisions on how we may direct limited drug development resources to the most promising treatments without wasting time and effort on the development of drugs that have little chance of changing patients’ lives for the better once they enter clinical testing.
- Finally, the research team has initiated molecular analysis aimed at identifying biomarker targets for treatment by extracting RNA, DNA and protein from the cell lines for whole genome sequencing. Genome-wide analyses of the 34 cervical cancer cell lines will provide a comprehensive and broadly accessible source of molecular information for the development of therapeutic avenues in cervical cancer. Through publication, this data will be shared around the world with other cervical cancer researchers and their respective labs.
The Fournier Fund could provide vital support for the following research efforts:
- Continue to fully incorporate the additional 20 cervical cancer cell lines into the cell line panel. Completion of this project will meaningfully enhance the TORL cancer cell line panel that has been successfully utilized in the discovery, development and FDA approval of major cancer drugs including Herceptin™ for HER2 positive breast cancer and Ibrance™ for hormone receptor positive breast cancer.
- Continue the work noted above with more extensive drug screens; testing of a total of 200 compounds is planned over the next year.
- Complete drug screening on the existing 14 cell lines
- Initiate screening using the additional 20 cell lines in order to achieve complete data sets across all 34 cell lines.
- Begin combination studies to identify synergistic drug combinations of new effective agents with existing established treatments such as chemotherapy or radiation therapy.
- Commence in vivo studies, once a sensitivity is determined, to confirm and validate lead compounds that have the potential to be clinically tested.
- Perform comprehensive cell line characterization including whole genome sequencing, RNA sequencing, methylation arrays and proteomic analyses on all 34 cell lines for the most comprehensive molecular characterization to date.