Scientists discover how to beat resistance to standard leukaemia drug
7 December 2011 - ICR scientists have revealed a technique to kill chronic myeloid leukaemia (CML) cells that have stopped responding to the current standard therapy.
A team led by Professor Richard Marais showed that combining the drug nilotinib (Tasigna) with another type of drug in early development, MEK inhibitors, destroyed CML cells that were no longer responding to standard treatment imatinib (Glivec).
Imatinib and nilotinib kill CML cells by blocking a strong molecular survival signal keeping them alive. The drugs are designed to fit snugly into a protein called BCR-ABL – like a key into a lock – in order to ‘lock up’ BCR-ABL and prevent it from triggering the survival signal in the first place.
In some cases BCR-ABL changes its shape and imatinib and nilotinib can no longer fit their ‘key’ into BCR-ABL’s ‘lock’. The survival signal remains switched on – and these drugs are powerless to turn it off. Survival for these cells means uncontrolled cell growth – the root of cancer.
The scientists revealed that a second set of molecular ‘keys’ – drugs called MEK inhibitors – can lock up a protein called MEK, the final checkpoint in the chain of proteins controlling the survival signals.
Nilotinib seems to make resistant cancer cells more responsive to the effects of MEK inhibitors and so the combination of treatments could kill these resistant cells
The research suggested that using MEK inhibitors alongside nilotinib would overcome CML resistance to imatinib and nilotinib.
“Acquired drug resistance is a significant problem in treating chronic myeloid leukaemia, so we’re very pleased to have found a potential strategy to overcome this. The next stage is to develop MEK inhibitors further and run clinical trials to see if they can be effective in patients,” Professor Marais said.
