Researchers from Trinity College Dublin have identified a new way of killing leukaemia cells, including those resistant to current therapies. The researchers describe how a new drug, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), is able to kill chronic lymphocytic leukaemia (CLL) cells, including those from patients with poor prognosis. PBOX-15 is one of a number of PBOX class of drugs which was developed by a team from Trinity College Dublin and the University of Siena. Researchers from the School of Medicine in collaboration with the School of Biochemistry and Immunology in Trinity College Dublin then tested the PBOX drugs in the laboratory and discovered that PBOX-15 is highly effective at killing CLL cancer cells, and at the same time spares normal cells. CLL is the most common leukaemia in the western world. While some progress has been made in developing new treatments for this disease, resistance and recurrence of the disease mean that new approaches need to be found.

"This important discovery is the result of a truly collaborative approach, involving researchers across the different disciplines of chemistry, biochemistry and molecular medicine at TCD, together with our colleagues in Siena and Belfast", said Professor Mark Lawler, School of Medicine, TCD and lead investigator on the study. "The complimentary expertise allowed us to approach the problem of killing CLL cells from a number of angles", he added.

The researchers showed that PBOX-15 is specifically active in cancerous cells and it works by interfering with the structure or architecture of the cancer cell. They also found that PBOX-15 activates key targets in leukaemia cells that triggers the cells to die. Cancer cells become resistant to chemotherapy by evading or avoiding cell death. The TCD researchers demonstrated that PBOX-15 can overcome this resistance and kill these cancer cells.

The researchers also conducted a laboratory study using CLL cells isolated from 55 CLL patients. PBOX- 15 was more effective than the front-line therapy, fludarabine, in killing CLL cells. The most exciting result was that PBOX-15 also killed CLL cells that were resistant to the existing treatment.

The ability of PBOX-15 to kill leukaemia cells while sparing normal blood cells suggests that the PBOX drug may pave the way for new approaches for the treatment of this incurable cancer.

Trinity College Dublin