Drug Screening Program
The Chordoma Foundation Drug Screening Program offers as a service to the research community rapid and cost-effective evaluation of promising therapies in preclinical models of the disease. A cornerstone of the Foundation’s Research Roadmap, this service provides crucial data needed to justify clinical trials and lowering the barrier to translating insights about chordoma into better treatments for chordoma patients. This service enables individual research groups to rapidly evaluate therapeutic concepts in-vivo without the time or expense of acquiring and expand mouse models. Additionally, banking models centrally and conducting multiple screening experiments in parallel affords significant cost savings through economies of scale.
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 Chordoma Foundation contracts with START to bank and expand a collection of patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models, and to conduct in-vivo experiments. 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 nuclear expression of brachyury, a defining marker of chordoma.
|Disease Status||Adult(>19) /Pediatric|
In the spirit of open science, figures displaying results from the Drug Screening Program are made available online through a collection on figshare, a digital repository that enables data to be easily cited, shared and discovered. Data is also summarized in the table below and can be viewed or downloaded as a Google Sheet for additional analysis. Data from internally nominated drugs are released immediately, whereas data from externally nominated drugs are released after publication or expiration of a pre-agreed embargo period.
CF study numbers in the above table indicate distinct experiments, each with multiple treatment arms and one control arm. Studies with an asterisk (*) indicate a shortened dosing period as opposed to dosing until the end of the study. Tumor Growth Inhibition (TGI) is expressed as the percent reduction in growth of tumors in drug-treated cohorts relative to control cohorts within the same study. The maximum TGI of 100%, indicates either no growth or tumor regression in the drug-treated cohort.
Results from the Drug Screening Program appear in the following publications:
- Rapid and Efficient Evaluation of Drug Sensitivity in a Diverse Panel of Chordoma Xenograft Models – 2018 (AACR poster)
- Afatinib is a new therapeutic approach in chordoma with a unique ability to target EGFR and Brachyury– 2017
- EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen – 2016
- Establishment and characterization of a panel of cell-based and patient-derived chordoma tumor models – 2016 (AACR poster)