Drug Screening Program
The Chordoma Foundation Drug Screening Program offers a centralized drug screening service to rapidly and cost-effectively assess the efficacy of potential new treatments for chordoma in preclinical models of the disease. A cornerstone of the Foundation’s Research Roadmap, this service enables efficient preclinical evaluation of promising therapies, providing crucial data needed to justify clinical trials and lowering the barrier to translating insights about chordoma into better treatments for chordoma patients.
This service eliminates the need for individual research groups to acquire, establish, and expand mouse models on their own, reducing time to set up drug screening experiments by a minimum of twelve months. Banking models and conducting screening centrally further affords significant cost savings because the expense of establishing and expanding the models is only incurred once, rather than each time a different research group wants to test a drug. Additional cost savings are realized through economies of scale provided by the ability to screen several compounds in parallel.
How it works
The Drug Screening Program is operated through a partnership with South Texas Accelerated Research Therapeutics (START), a San Antonio-based contract research laboratory that specializes in preclinical cancer drug development. The Foundation contracts with START to develop, bank, expand, and test patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models.
The Foundation continually identifies promising therapeutic approaches to test based on evidence in the literature and emerging findings from grantees and collaborators. Additionally, the Foundation accepts proposals for therapies to test from researchers in academia and industry. On an ongoing basis, the Foundation’s Scientific Advisory Board vets and prioritizes therapeutic approaches nominated internally as well as by external researchers.
Results from testing internally-nominated drugs are made public following completion of the experiments to enable researchers and companies to act upon these findings as quickly as possible. Results from externally-nominated drugs are shared with the collaborating research group or company under pre-agreed terms of data sharing.
Patient-derived xenograft (PDX) models and cell line-derived xenograft models (CDX) available for screening are shown in the table below. All models are rigorously validated to confirm chordoma-consistent histology and the presence of brachyury, a protein highly expressed in chordoma tumors.
|U-CH1||CDX||University of Ulm||Available|
The following table summarizes data generated from the Drug Screening Program. This table is updated on an ongoing basis as more results from in vivo drug testing become available. The information in the table includes:
- Drug target selected from supporting evidence that demonstrates a role for this target in chordoma (See description of Therapeutic Targets at: chordomafoundation.org/targets/)
- Drug tested
- PDX or CDX model used
- CF study number in order to identify drugs tested in the same experiment
- Tumor Growth Inhibition (TGI) expressed in percent comparing the growth of tumors in drug-treated animals to the growth of tumors in control, untreated animals with the corresponding p-value considered statistically significant if p<0.05
Using data visualization software from Tableau, data in this table can be sorted by both target and drug class. Furthermore, the data from the table can be viewed and downloaded as a Google Sheet for additional analysis.
CF study numbers with an (*) in the table above indicate a 28 day dosing period as opposed to dosing until the end of the study.
Published results generated from the Drug Screening Program include:
- Establishment and characterization of a panel of cell-based and patient-derived chordoma tumor models – 2016 (AACR poster)
- EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen – 2016
- Afatinib is a new therapeutic approach in chordoma with a unique ability to target EGFR and Brachyury– 2017