Earlier this year, we announced the launch of the Foundation’s Drug Screening Pipeline, a program designed to rapidly and cost-effectively test new treatments in chordoma disease models, including cell lines (human tumor cells grown in a petri dish) and xenograft models (human tumors grown in mice). This was an important step because it provides researchers with a way to generate the preclinical proof of concept data needed to justify testing a treatment in patients and investing in a clinical trial. In other words, it helps bridge the divide between promising discoveries made in a lab, and new treatment options for chordoma patients.

Through this new program, we are currently testing more than a dozen drugs on behalf of six research groups and one company, and are planning to test an additional 10 drugs in the coming year. Preliminary results indicate that three classes of drugs – EGFR inhibitors, CDK4/6 inhibitors, and PI3K inhibitors – are capable of significantly slowing growth of chordoma tumors in mice.

While these results are very encouraging, they must be taken with a grain of salt. That’s because the drugs have thus far only been tested in two xenograft models – too few to make conclusions that can be generalized to all chordoma patients.

Given that each individual’s tumor is unique, it is important to test drugs in models derived from multiple tumors to determine whether findings are applicable to all chordoma patients, or just a subset. Hence, developing additional xenograft models is critical for confirming these initial findings, and uncovering more effective treatments for chordoma patients. Our goal is to develop a panel of at least 10 well-characterized xenograft models that represent the full range of behavior of chordomas in patients – including tumors in adults and children, skull base and spine, pre-treatment and post-treatment, etc.

More models on the way

We are taking a multi-pronged approach to developing additional xenograft models. First, we offer prizes to researchers who successfully create new models – including cell lines and xenograft models. This has resulted in the development of 12 new cell lines and 2 xenograft models.

While we have had significant success in spurring development of cell lines with prizes, developing xenograft models has proven more difficult because fewer researchers are equipped to do this work and the upfront cost is significantly higher for individual labs.

To speed up the process of xenograft development and increase the odds of success, last year we partnered with South Texas Accelerated Research Therapeutics (START) – a contract research laboratory specializing in preclinical cancer research – to create an industrial scale xenograft development pipeline. Through this program, tumor tissue donated by chordoma patients is implanted directly into mice to attempt to develop new xenograft models. Any resulting models will be included in our Drug Screening Pipeline and also made freely available to the research community. Our goal is to engraft 50 tumors by the end of 2017.

In the past year, we have engrafted more than 20 tumors in mice. Because chordoma is slow growing, the process from tumor engraftment to usable model takes one to three years, and, based on the experience of other researchers, we expect the success rate to be less than one in five. However, we are seeing exciting early signs of progress. Already, two of the implanted tumors have grown very well and are nearly ready to be used for drug testing. They are currently being validated to ensure that they faithfully mimic the tumor from which they were derived. Other engrafted tumors are growing as well, albeit more slowly, and each month we engraft several more tumors contributed by chordoma patients across the country.

Tumor donation is critical to success

Developing new xenograft models depends upon chordoma patients choosing to donate their tumor tissue at the time of surgery. Our Tumor Donation Program makes this process simple for patients.

If you are planning to have surgery, simply contact me at tumordonation@chordoma.org and, with your permission, I will work with your care team to obtain any excess tumor that is left over after surgery. Samples collected through the Tumor Donation Program are stored in our centralized tissue repository – “The CF Biobank” – for use by researchers across the world. And, whenever logistically possible, a portion of the collected tumor will be used to attempt to develop a new chordoma xenograft model.

While our Tumor Donation Program has successfully collected tumor tissue from more than 30 hospitals over the past four years, obtaining live tissue required to create a xenograft model can be logistically complex and requires significant coordination and cooperation on the part of the care team. We have found that it is the most successful when there is an internal champion at the hospital who is committed to helping patients participate in research. Often operating behind the scenes, these nurses and research coordinators are the unsung heroes of medical research.

In the past year, two such individuals have played an outsized role in the success of our efforts to develop new xenograft models: Roberta Sales, a nurse in the orthopedic oncology service at Memorial Sloan Kettering Cancer Center, and Benita Valappil, clinical research director of the Center for Cranial Base Surgery at the University of Pittsburgh Medical Center. Each of them works to ensure that tumor is collected from every patient who wishes to contribute, and, together, they are responsible for nearly two-thirds of the samples that have been engrafted in our xenograft development pipeline.

We owe a great debt of gratitude to Roberta and Benita and to all of the other doctors, nurses, and hospital staff who have made this effort possible. But, above all, we are grateful to the patients who have donated their tumor tissue to help advance the search for a cure. Their contributions are helping to give researchers the tools they need to bring treatments to the clinic faster. Our goal now is to engraft an additional 20 tumors in mice within the next year. Once we do, we will be well on the way to alleviating one of the most significant remaining barriers to developing new treatments for chordoma.