Two papers have been published in the last fortnight announcing big steps forward in the fight against leukemia, both anchored by the same research institution. The studies are at very different stages of tackling the two most common forms of the cancer, but both offer hope.
On January 28 the New England Journal of Medicine announced the results of a trial of 116 patients with chronic lymphocytic leukemia (CLL), a cancer in which leukemic white blood cells accumulate. As the paper noted, “New treatments have improved outcomes for patients with relapsed CLL, but complete remissions remain uncommon.”
However, the patients in the trial were given Venetoclax, a drug that targets the BCL2 protein, which the paper describes as “central to the survival of CLL cells.”
Patients were given between 150 and 1,200 milligrams of Venetoclax a day. Despite the fact that 89 percent had “poor prognostic clinical or genetic features” entering the trial, responses were good, with 20 percent showing complete remission. Side effects included mild diarrhea, upper respiratory tract infection and nausea, but each of these applied to only around half the patients. Results were even better for the 60 patients who joined the study later and were given doses of up to 400 milligrams, which data from the initial 56 patients suggested was optimal.
The results are a big boost for the Walter and Eliza Hall Institute (WEHI), which discovered the role that BCL2 plays in some cancers and has been central in the long quest to find a way to block it.
Two weeks earlier WEHI announced that the Hhex protein is a promising target in efforts to treat acute myeloid leukemia (AML). AML is slightly rarer than CLL, but strikes at a somewhat younger age, with a median age of diagnosis of 63, compared to CLL's 70.
The five-year survival rate for AML is just 24 percent.
“There is an urgent need for new therapies to treat AML,” said WEHI's Dr Matt McCormack in a statement. “We showed blocking the Hhex protein could put the brakes on leukaemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”
Hhex is overproduced in AML cells, giving plenty of opportunities for drugs that might target it. “Most existing treatments for AML are not cancer cell-specific, and unfortunately kill off healthy cells in the process,” Dr McCormack said. “Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side-effects that come with standard cancer treatments.”
McCormack is the senior author of a paper in Genes and Development that describes the method by which Hhex represses growth control genes, which prevent damaged cells from reproducing and thus potentially forming cancer.
To replicate their success against CLL, McCormak said, “We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”