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Researchers have been struggling for years to find a cure for patients with recurrent acute myeloid leukemia (AML), an aggressive blood cancer that is one of the deadliest cancers. About 19,520 new cases are diagnosed each year and about 10,670 people die each year, according to the American Cancer Society.
Researchers at Purdue University are developing a series of drug compounds that have shown promise for treating such cases. About 30% of patients with AML have a mutation that is caused by a kinase called FLT3, which makes leukemia more aggressive. FLT3 inhibitors, such as Radapt, approved last year by the US Food and Drug Administration, have shown a good initial response to leukemia treatment. Gelatinib, another FLT3 inhibitor, has recently been approved by the end of 2018. However, FLAM-3 inhibitor-treated LAM patients often relapse due to secondary FLT3 mutations, and existing therapies are not available. have not fully managed to treat these cases.
Researchers from a team led by Herman O. Sintim, a chemistry professor in the Drug Discovery chemistry department at Purdue, said they have developed a series of compounds that not only act on the LMA with the common FLT3 mutation, but also on drug-resistant LMA mutations, such as the F691L gatekeeper mutation, in some leukemic relapsing patients.
"These compounds have great potential to become the next-generation LMA therapy for relapsed patients who no longer respond to first- or second-generation FLT3 inhibitors," Sintim said.
The results of the study were published Friday in the journal EBioMedicine.
The research aligns with the celebration of Purdue's giant leaps, recognizing the global advances made by the university in health, longevity and quality of life as part of Purdue's 150th anniversary. This is one of the four themes of the Celebration Ideas Festival, which aims to introduce Purdue as an intellectual center for solving concrete problems.
The results of the study are encouraging because although many other forms of cancer have progressed over the last three decades, the progress of the AML has been slow.
AML, which accounts for only about 1% of all cancers, occurs when blood cells fail to mature or differentiate and do not multiply, resulting in a lack of red blood cells that carry the disease. oxygen. AML is rare before the age of 45, but it occurs in children. The five-year survival rate is about 30%, and in patients over 65, the five-year survival rate is less than 10%.
The compounds studied by Purdue researchers, alkynylaminoisoquinoline and alkynylnaphthyridine, have been proven in preclinical studies, Sintim said. "In studies in mice, the burden of leukemia was hardly noticeable after compound treatment for only a few weeks.This new clbad of FLT3 inhibitors also works against secondary drug mutations. -resistant, such as the problematic mutatio F691L ", said Sintim.
In the clinic, the goal is to reduce leukemia levels enough for a patient to undergo a bone marrow transplant. Most often, if the burden of leukemia is not significantly reduced before bone marrow transplantation, the risk of recurrence of AML is high.
Sintim said the compounds developed by the researchers showed no signs of toxicity. Observations made during clinical trials show that high doses of the compounds do not cause weight loss, irritability or dysfunction of vital organs. Another advantage of the compounds developed by Purdue researchers is that they can be taken orally, which makes it easier for patients to take home compared to an injection.
Sintim said that there was still much to learn about the LMA.
"Acute myeloid leukemia is not caused by a single mutation, it is caused by multiple mutations, which means that you may have a patient with acute myeloid leukemia who has a type of mutation and you may have one. another with another type of mutation and you can not give them the same medicine.Although a patient initially has a type of mutation, a new mutation may appear during treatment, "he said. "So, to effectively treat a cancer, you need to know what is the aligned mutation.This is what is called precision medicine: adapting a drug to a particular pathogen."
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Material provided by Purdue University. Original written by Tom Coyne. Note: Content can be changed for style and length.
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