Potential treatment for T-ALL in the pipeline
MedWire News: Scientists have identified two enzymes - phosphoinositide 3-kinase (PI3K) γ and δ - that are associated with T cell acute lymphoblastic leukemia (T-ALL).
The team demonstrated that these enzymes could be inhibited by CAL-130 and therefore survival prolonged in a mouse model of T-ALL.
"Clearly, we have a drug that is extremely effective against this type of cancer in mice," said study author Thomas Diacovo (Columbia University Medical Center, New York, USA) in a press statement.
"If this treatment strategy can safely and selectively target the activity of these enzymes in T-ALL tumors, we might be able to reduce the need for conventional chemotherapies that more broadly affect proliferating cells, including those in healthy tissues. This would be a major advancement in helping to reduce drug toxicities in young patients," he added.
Previous research by Diacovo and team showed that PI3K gamma and delta reduce inflammation and cause death of developing T cells.
Hypothesizing that these enzymes could be implicated in the development of T-ALL, the investigators found that in mice with an inactive version of the PTEN tumor suppressor gene, both PI3K gamma and delta-triggered leukemogenesis.
However, if the function of the two enzymes was inactivated, tumor formation was suppressed.
As reported in Cancer Cell, the team found that when mice with T-ALL were injected with a dual inhibitor of PI3K gamma and delta known as CAL-130, disease burden was reduced and survival was prolonged.
They explained that the level of circulating leukemia cells dropped from a mean of 100 million per mL to less than 1 million per mL 24-48 hours after CAL-130 was administered to the mice.
In addition, after 7 days of therapy, survival time in mice treated with CAL-130 was 45.0 days on average, compared with 7.5 days for untreated controls.
"We've made great strides in treating childhood acute lymphoblastic leukemias over the years, with an overall cure rate approaching 90 %," said Diacovo.
"Unfortunately, this is not the case for T-ALL. In addition, conventional treatment - chemotherapy - is quite toxic. This is a particular problem for children, who have an entire lifetime ahead of them and are likely to develop secondary cancers and other complications as a result of their treatment. So anything we can do to lessen associated toxicities would be a welcome advancement in the field."
By Helen Albert