|Awarded On||August 24, 2018|
|Title||TREX2 Inhibitors to Treat BCR-ABL-Cancers|
|Award Mechanism||High Impact/High Risk|
|Institution/Organization||The University of Texas Health Science Center at San Antonio|
|Principal Investigator/Program Director||E. Paul Hasty|
|Cancer Sites||Leukemia, Myeloma|
BCR-ABL is generated from the improper fusion of two genes. This protein has unregulated activity that can increase genomic mutations and the risk to cancers like leukemia. Tyrosine kinase inhibitors (TKIs) are drugs that effectively treat BCR-ABL-expressing cancers. However, BCR-ABL has a negative influence on DNA repair that leads to genomic mutations and these mutations can cause resistance to TKIs. I propose to test a novel approach to fight TKI resistance that combines the use of TKIs with TREX2 inhibitors (TX2Is), a new class of drugs developed in my lab. I hypothesize that BCR-ABL induces genomic mutations by reducing the capacity of two DNA repair pathways called homologous recombina...