According to findings presented at the American Association for Cancer Research special conference Hematologic Malignancies: Translating Discoveries to Novel Therapies in Philadelphia, Pennsylvania, CX-5461, an investigational drug that inhibits RNA polymerase 1 (Pol 1) may improve survival for patients with highly aggressive acute myeloid leukemia (AML).
Researchers tested CX-5461 in animal models with AML with MLL gene rearrangements and multiple myeloma refractory to standard therapy. Efficacy was found to be independent of tumor protein p53 status. According to Ross D. Hannan, PhD, head of the Oncogenic Signaling and Growth Control Program at the Peter MacCallum Cancer Centre in Melbourne, Australia, Pol 1 levels are usually increased in cancers, especially hematologic malignancies like B-cell lymphoma. Therefore, the protein may be a good target for CX-5461, which blocks Pol 1.
Hannan and his colleagues found that CX-5461 extended prolonged overall survival in mice with MLL/ENL + Nras AML, a highly aggressive form of AML. Specifically, median survival time for mice treated with CX-5461 was 36 days, while mice treated with cytarabine in combination with doxorubicin was 21 days. Mice treated with no drug had a median survival of 17 days.
The investigational drug CX-5461, which blocks the protein RNA polymerase I (Pol I), prolonged survival in mouse models of highly aggressive acute myeloid leukemia (AML) and multiple myeloma, according to data presented at the American Association for Cancer Research special conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, held Sept. 20-23.
“Some forms of AML and multiple myeloma are highly refractive to standard therapies,” said Ross D. Hannan, PhD, head of the Oncogenic Signalling and Growth Control Program and a professor at the Peter MacCallum Cancer Centre, Melbourne, Australia. “There is an urgent need for new drugs that can treat patients with these cancers that have relapsed on standard therapy, which is why we chose to study the effects of CX-5461 in mouse models of these diseases.