Dr. Chandrika Gowda
Research Grant Update
Researcher – Dr. Chandrika Gowda
We are grateful to TeamConnor for the continued support of our work, which aims to identify children with high-risk AML with specific gene rearrangements with poor prognoses. Our focus is on the KMT2A/MLL rearranged AML children known to have a high rate of treatment failure. Our initial findings showed that among all AML cases, the ones with MLL rearrangement were more sensitive to inhibition of a protein called CK2. We used a novel drug in clinical development called CX-4945. We showed that using CX-4945 in combination with chemotherapy drugs like cytarabine, daunorubicin, and venetoclax can help prevent and overcome resistance to those drugs and prevent disease relapse. We have now completed experiments showing the therapeutic efficacy of CX-4945 with two commonly used chemotherapy drugs, cytarabine, and venetoclax.
The next logical step that will be undertaken in the next few months is understanding the underlying mechanism that makes this drug combination so effective. We have planned experiments to understand better how mice handle the combination treatment without added toxicity and determine how safe this combination is for translation to human studies. Another exciting progress in this regard is our recent meeting with the pharmaceutical company that produces CX-4945, who were equally excited about the promising results and agreed to provide the drug for further testing in mice and humans soon. As we prepare to take these findings to clinical testing, we also explore newer and more potent CK2 inhibitor compounds. We are testing one such compound that was provided to us by another pharmaceutical company which has shown a significant anti-leukemia effect in AML cells. Overall, we are very excited about the progress and direction of this project. Continued support from TeamConnor has significantly expedited the animal studies that form the basis for human testing.