Chordoma Foundation

New Drug Screening Pipeline streamlines translational research

We are pleased to announce the launch of the Chordoma Foundation Drug Screening Pipeline, a centralized platform designed to rapidly and cost-effectively assess the efficacy of potential new treatments for chordoma in preclinical models of the disease.

The accelerating pace of progress in chordoma research has resulted in the discovery of an ever-increasing number of potential therapeutic targets and corresponding therapies that could hold promise for chordoma. Therapies of interest range from early-stage investigational agents through FDA-approved drugs. The primary means of evaluating the therapeutic potential of these agents prior to embarking on human clinical trials is through drug sensitivity testing in preclinical disease models – in particular, human tumors grown in specialized mice (called xenograft models).

However, the substantial up-front investment of time and resources required for preclinical experiments represents an often insurmountable burden for academic and industry laboratories alike, stalling the translation of research findings into new treatments for patients. In an effort to substantially reduce this burden and accelerate treatment development, the Foundation has created a new centralized drug screening platform in collaboration with South Texas Accelerated Research Therapeutics (START), a San Antonio-based contract research laboratory that specializes in cancer drug development. Last week, at the American Association of Cancer Research (AACR) annual meeting in New Orleans the Chordoma Foundation and START jointly presented a poster describing this new program.

Through this program, tumor models are developed, banked, and expanded at START, eventually providing enough mice to test up to 20 drugs or drug combinations per year. Initially, the Foundation is working to test promising therapeutic approaches identified based on evidence in peer-reviewed publications (see Target Dashboard) as well as emerging findings from grantees and collaborators. In the near future, the Foundation will begin soliciting and accepting drug screening proposals from researchers in academia and industry. On an ongoing basis, the Foundation’s Scientific Advisory Board will vet and prioritize therapeutic approaches nominated internally and by external researchers.

Currently, two different chordoma mouse models are available for screening, including one patient derived xenograft (PDX) model and one cell line derived xenograft model. The Foundation is collaborating with START to develop additional models and is also offering a prize to researchers who successfully develop new models. All models used for screening are rigorously characterized to ensure that they maintain molecular and genetic features typical of chordoma and consistent with the patient tumors from which they were derived. Eventually, the Foundation aims to develop a panel of chordoma tumor models representing the diverse clinical manifestations of the disease to ensure that results are broadly applicable to the chordoma patient community.

This resource eliminates the need for individual research groups to acquire, establish, and expand chordoma models on their own, reducing time to initiate drug screening experiments by a minimum of twelve months. Centralizing model banking and drug screening further affords significant cost savings by eliminating redundant expenses and efforts in multiple labs. Additional cost savings are realized through economies of scale provided by the ability to screen multiple drugs in parallel.

The first set of drug screening experiments are currently underway and initial results will be available in the coming months. Data from testing internally nominated drugs will be made available online through figshare, a digital repository of scientific data, to enable researchers to build upon these findings as quickly as possible. Data from externally nominated drugs will first be shared with the collaborating researchers to enable them to include results in a peer-reviewed publication.

In the coming year, the Foundation aims to complete testing of a minimum of ten drugs. Identification of preclinical efficacy in any of these studies could provide rationale to pursue a clinical trial for chordoma patients. Going forward, as resources become available, more drugs will be tested, eventually creating a stream of preclinical proof-of-concept data to justify future clinical trials.

To find out more about the Drug Screening Pipeline and opportunities to support this important program please contact Executive Director, Josh Sommer at josh@chordoma.org.