Drug Screening Program
The Chordoma Foundation’s Drug Screening Program provides the research community with a rapid and cost-effective means of evaluating promising therapies in preclinical models of chordoma. It is operated in partnership with South Texas Accelerated Research Therapeutics (START), a San Antonio-based contract research laboratory that specializes in preclinical cancer drug development. Centralizing these experiments in a single laboratory creates efficiencies which significantly reduce the time and cost of generating preclinical data, thereby lowering the barrier to moving promising drugs into clinical trials and translating insights about chordoma into better treatments for chordoma patients.
How it works
Drugs are nominated for testing through two approaches. First, proposals are accepted and reviewed on a rolling basis from researchers in academia and industry. Additionally, the Foundation’s staff and Scientific Advisory Board proactively identify promising therapeutic approaches to test based on evidence in the literature and emerging findings from grantees and collaborators. Experiments are designed and overseen by Chordoma Foundation Director of Research, Dr. Joan Levy, and carried out at the Foundation’s direction by START. Data generated from internally nominated drugs are made public immediately, while results from externally nominated drugs are shared according to pre-defined data use agreements.
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.
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:
- Rationale for the advancement of PI3K pathway inhibitors for personalized chordoma therapy – 2020
- 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)