Drug's 'double hit' overcomes leukaemia resistance

ICR scientists have discovered a unique drug that uses a ‘double hit’ to kill acute myeloid leukaemia (AML) cells.

Around 30 per cent of patients with AML have faults in the FLT3 gene, which are linked to more aggressive leukaemias and poor survival. While drugs that target these faults are available, the disease eventually builds resistance, leaving treatments ineffective.

To combat this, researchers developed a drug that blocks both the protein made by the faulty FLT3 gene along with another key protein called Aurora kinase, which are both involved in driving cancer growth. The drug is also unique because it can destroy cells even if they develop new faults in the FLT3 genes that would make them resistant to other inhibitors.

The combination led to complete remission in half of the mice treated with this drug, compared with only 25 per cent with an existing drug that only blocks FLT3.

Dr Spiros Linardopoulos, leader of the ICR’s cancer drug target discovery team said: “There has been great interest in using FLT3 drugs to treat AML, but their effectiveness has been limited because leukaemia cells gain new mistakes in the FLT3 gene, causing resistance.

“Our new drug has the potential to overcome this and has a range of possible uses in AML – as a first line of attack for patients with faulty FLT3, in particular in those over 60 who don’t tolerate chemotherapy well, and also to treat leukaemia patients who have relapsed.”

The study published in the journal Leukemia.