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New Drug Compounds to Spearhead Next Generation Leukemia Treatments

One of the biggest concerns with acute myeloid leukemia (AML) is the high risk of recurrence.  This aggressive form of blood cancer carries a particularly poor prognosis and each year affects the lives of more than 20,000 people, according to estimates from the American Cancer Society. In about 30% of cases, AML is triggered by [...]

One of the biggest concerns with acute myeloid leukemia (AML) is the high risk of recurrence.  This aggressive form of blood cancer carries a particularly poor prognosis and each year affects the lives of more than 20,000 people, according to estimates from the American Cancer Society.

In about 30% of cases, AML is triggered by mutations caused by a kinase called FLT3, which makes leukemia more aggressive.  While there are several effective FLT3 inhibitors approved by the FDA, like Radapt or Gilteritinib, patients often experience a return of their disease as a result of secondary mutations.

Purdue University researchers are now focusing their efforts on developing several drug compounds which have shown promise not only against the more common FLT3 alteration, but also drug-resistant AML caused by other problematic mutations, such as the gatekeeper F691L variation.

Acute myeloid leukemia is not caused by only one mutation.  It’s caused by many mutations.  What that means is that you might have an acute myeloid leukemia patient who would have one type of a mutation and you could have another one with another type of mutation and you cannot give them the same drug”, explained Herman Sintim, Professor of Chemistry at Purdue.  “So to effectively treat a cancer you need to know what the aligning mutation is, this is what is called precision medicine; tailoring a drug to a particular disease driver”.

AML occurs when blood cells fail to mature or differentiate and divide uncontrollably, causing a lack of adequate oxygen-carrying red blood cells.  The disease rarely manifests in patients younger than 45 years, but can appear in children.  Only about 30% of cases survive the initial five years after diagnosis, while patients over the age of 65 have a five-year survival rate of less than 10%.

The compounds that are currently examined are alkynyl aminoisoquinoline and alkynyl napthyridine, both producing successful responses in preclinical studiesThey have exhibited no signs of toxicity and presented no weight loss, irritability or essential organs dysfunction.  Another big advantage is the fact that the compounds can be taken orally, making them easier to administer.

These compounds have a great potential to be the next-generation AML therapeutics for relapsed patients who no longer respond to first- or second-generation FLT3 inhibitors, noted Dr.  Sintim.

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