Modulating the immune response and enhancing DNA damage in Ewing sarcoma by inhibiting ENPP1
Ewing sarcoma is an aggressive cancer that is difficult to treat when it recurrs or when it has metastasized. We have discovered a potentially novel therapeutic approach targeting a protein called ENPP1. This protein appears to have dual roles in Ewing sarcoma. On the one hand, it potentially can alter the immune repsonse to Ewing sarcoma, helping to reactivate the immune system to attack the cancer. On the other hand, ENPP1 also appears to be involved in the response to DNA damage. As DNA damage can also be targeted by chemotherapy or by a type of drug called a PARP inhibitor. we propose to test the utility of combining ENPP1 inhibition with PARP inhibition to treat Ewing sarcoma.
Project Goals
Our goals are:
1)to understand the molecular function of ENPP1 in Ewing sarcoma and especially to understand the role of ENPP1 in mediating response to DNA damage.
2)to test the use of a novel ENPP1 inhibitor which is in clinical development and to determine whether it is effective to treat Ewing sarcoma metastasis.
3)to test the use of combining ENPP1 inhibitors and PARP inhibitors as a novel combination therapy for Ewing aarcoma.
