We have known for many years that Ewing’s sarcoma arises when cell division goes wrong, creating a translocation which brings together a portion of chromosome 11 with a portion of chromosome 22. The resulting translocation creates a new sequence of DNA which instructs the cell to become malignant. This mechanism of translocation is the basic mechanism which leads to cancer for dozens of sarcomas.
For over two decades we have been trying to find a way to target this abnormal sequence of DNA to reverse the process which transforms normal cells into cancer cells. The DNA sequence is buried deep inside the cell nucleus and it has been very hard to find a way to attack it. Dr. Jeffrey Toretsky found a compound that worked in the test tube, and we began a clinical trial of the investigational compound TK-216.
We have now seen a patient with Ewing sarcoma whose disease had relapsed three times, for whom chemotherapy was not working, respond to this novel compound. This is the first time we have ever successfully targeted a chromosome translocation which is responsible for the emergence of cancer. Since we presented these results at the international meeting in November, 2019, we have seen three additional patients respond to this ground breaking therapy.