The investigators will refine their new model for evaluating the ability of experimental treatments to curtail growth of deadly brain tumors called gliomas. The new treatment evaluation method, if successful, will provide a faster and easier route for progressing from preclinical animal testing to clinical trials in humans, an important advance since gliomas are usually fatal within a year.
Currently, glioma treatments are tested in animals using a time-and-cost-intensive method. The testing requires that tumor cells be injected in mouse brains. MRI imaging is then used over time to view the extent of tumor growth during treatment with experimental therapies. The greater the tumor cell growth, the less effective is the therapy. The Dana-Farber investigators hypothesize that they have a faster, cheaper, and easier way to evaluate glioma treatment effectiveness in animal models.
These investigators have genetically engineered glioma cells to emit light that can be detected by a sensitive low-light camera. Now, the researchers will refine this technique to provide an optimal method for modeling brain tumors in mice. This method first entails using genomic analysis to determine whether growing tumor cells in the laboratory or using cells obtained directly from glioma patients produces an animal model that most closely resembles the human disease.
Next, the researchers will determine how this new imaging technique can be used to identify the molecular characteristics of tumor cells that respond to the signals that direct them to continue to grow. To achieve this aim, investigators will create the capacity for the tumor cells to emit light in a stimulus-specific manner. The greater the intensity of the stimulus to continue growth, the greater the amount of light that is emitted. In this way, the researchers will be able to assess the effectiveness of various therapies that are designed to inhibit these growth-promoting signals. Those therapies that hit growth-promoting signal targets and inhibit them will cause lower levels of light to be emitted by the tumor cells. If this technique works, the investigators will plan to seek funding from other sources to evaluate the effectiveness of various experimental therapies in hitting a target they have identified that produces growth-promoting signals.
Significance: If investigators can effectively use light emission by tumor cells as a reflection of the strength of signals that direct the tumor cells to grow, this new method will accelerate animal tests of new anti-tumor therapies. Faster animal test results will facilitate earlier testing of promising therapies in humans. Since gliomas are quickly fatal, this acceleration from animal to human testing is critical.