This week we profile a recent publication in Nature Medicine from the laboratory of
Dr. Jim Olson (fourth from right) at Fred Hutchinson Cancer Research Center.
Can you provide a brief overview of your lab’s current research focus?
Our team focuses on pediatric brain tumor therapeutics and the discovery of novel peptide therapeutics for a variety of diseases. We discovered “Tumor Paint”, a scorpion-derived peptide that delivers fluorescent markers to cancer cells. Stemming from that work, the investigational agent Tozuleristide (Blaze Bioscience) is now entering a nationwide clinical trial that could potentially lead to FDA registration. We are now using the patient-derived mouse models described in the Nature Medicine paper to prioritize treatment strategies for the types of brain tumors that most often lead to death in children. A key component of this work is to assess drugs in mice that have previously had radiation therapy to the cancer. Too often, drugs that look promising in radiation- or chemotherapy-naïve models are advanced to Phase I/II trials in human patients who previously had radiation therapy and/or chemotherapy, which often results in therapy resistance mechanisms that are absent in treatment-naïve mouse models.
What is the significance of the findings in this publication?
In the past, pre-clinical studies typically relied on one or two mouse models that, at best, represented one or two patients. At worst, the “workhorse” models did not represent any patients because the cells had been grown on plastic and fed with bovine serum, which changes the biology dramatically. In this study, we took specimens of brain tumors directly from the operating room at Seattle Childrens Hospital, rushed them over to Fred Hutch, and implanted them in the brains of mice that were genetically programmed to not reject the human tumor cells. As a result, we now publish 30 patient-derived mouse models that have been fully genomically characterized and are known to properly represent the biology of the 30 patients from whom they were derived. In some cases, these are the only mouse models in the world of a particular type of pediatric brain tumor. We make all of these available to investigators around the world with no strings attached through our website www.btrl.org.
What are the next steps for this research?
In addition to the 30 patient-derived mouse models that we published, we are characterizing more than 20 others. The next steps are focusing on converting these mouse models into models that better represent patients who are entering Phase I/II clinical trials by pre-treating the mouse tumors with radiation, chemotherapy or both.
This research was funded by:
The majority of funding came from the Pediatric Brain Tumor Research Fund Guild through the Run of Hope that they sponsor each September at Seward Park. Additional funding came from the National Cancer Institute.
