Scientists discover how to beat resistance to standard leukaemia drug

December 9, 2011, Cancer Research UK

(Medical Xpress) -- Cancer Research UK-funded scientists at The Institute of Cancer Research (ICR) have revealed a technique to kill chronic myeloid leukaemia (CML) cells that have stopped responding to a targeted drug, according to research published in Cancer Cell today.

The team carried out the research in CML . They showed that drugs currently in early development, called MEK inhibitors, combined with nilotinib (Tasigna) destroyed CML cells after they had stopped responding to imatinib (Glivec), the current standard treatment for CML.

Imatinib and nilotinib kill CML cells by blocking a strong molecular signal keeping them alive. The drugs are designed to fit snugly into a protein called BCR-ABL – like a key into a lock – so as 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 .

But the revealed that a second set of molecular ‘keys’ – drugs called MEK inhibitors – can lock up a called MEK, the final checkpoint in the chain of proteins controlling the survival signals.  Nilotinib seems to make resistant more responsive to the effects of MEK inhibitors and so the combination of treatments killed these resistant cells.

The research suggested that using MEK inhibitors alongside nilotinib would overcome CML resistance to imatinib and nilotinib.

Lead author, Professor Richard Marais from the ICR, said: “We are learning more about the molecular locks which have ‘seized up’, keeping survival signals turned on in CML cells. This important research shows that drugs currently in development can free these locks to switch off survival signals and destroy cancer cells.

“It’s exciting to discover that the MEK inhibitors can be used alongside nilotinib to kill CML cells that are no longer responding to or nilotinib alone. Acquired 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 further and run clinical trials to see if they can be effective in patients.”

There are more than 600 cases of CML diagnosed each year in the UK.

Dr. Julie Sharp, Cancer Research UK’s senior science information manager, said: “People diagnosed with leukaemia today are four times more likely to survive their disease beyond 10 years as those diagnosed in the early 1970s. And thanks to the generosity of the public we’ve been able to invest in research, which has been at the heart of this progress.

“This important discovery increases our understanding of how leukaemia cells respond to drugs and reveals a potential approach to treat the disease after it has become resistant to current treatments.”

More information: Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukaemia. Packer et al, Cancer Cell.

Related Stories

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.