Targeted Agent Appears Promising in Inducing Cancer Cell Apoptosis in Chronic Leukemia Model

December 9, 2009
Christina T. Loguidice

Current treatments for chronic lymphocytic leukemia (CLL) can be damaging to the immune system, leaving patients vulnerable to infections, which is the primary cause of death for many patients with CLL. According to a study presented at the 51st Annual American Society of Hematology Meeting, a new oral agent called 17-DMAG may avoid this problem. Mouse models assessing 17-DMAG showed this agent to be highly selective for CLL cells, while having minimal effect on normal immune cells, suggesting the agent leaves the immune system intact.

Current treatments for chronic lymphocytic leukemia (CLL) can be damaging to the immune system, leaving patients vulnerable to infections, which is the primary cause of death for many patients with CLL. According to a study presented at the 51st Annual American Society of Hematology Meeting, a new oral agent called 17-DMAG may avoid this problem.

Mouse models assessing 17-DMAG showed this agent to be highly selective for CLL cells, while having minimal effect on normal immune cells, suggesting the agent leaves the immune system intact. The agent works by deactivating several proteins that cancer cells need to survive, including HSP90, AKT, RAF, and Zap-70. According to Amy J. Johnson, MD, assistant professor, Division of Hematology and Oncology, Ohio State Comprehensive Cancer Center — James Cancer Hospital and Solove Research Institute, “We show that this activity occurs in both CLL cells from patients and in a CLL mouse model.”

The agent was also found to re-activate the FOX3D gene, which Dr Johnson and colleagues found in earlier studies to become silenced early during human CLL development, a change that is thought to contribute to CLL progression. Mice that were treated with 17-DMAG experienced significantly prolonged survival compared with those that were untreated, surviving 75 days versus 66 days (P =

.027). Another benefit of 17-DMAG is its oral formulation, which allows the agent to be administered by continuous dosing, allowing uninterrupted inhibition of HSP90. According to Dr Johnson, “Our findings strongly support testing this agent in CLL patients in a phase I clinical trial.” ASH Abstract 732

Disclosures:

Dr Johnson and colleagues had no conflicts of interest to disclose.