Blocking SMURFs may increase effectiveness of experimental melanoma drug

In collaboration with the Press Association

Lowering the levels of a protein called SMURF2 inside melanoma cells can boost the effectiveness of experimental drugs called MEK inhibitors, according to researchers in Manchester.

The discovery could ultimately lead to new trials aimed at overcoming resistance to these drugs, which can develop rapidly in melanoma patients on existing trials.

Dr Claudia Wellbrock and her team at the Wellcome Trust Centre for Cell-Matrix Research at Manchester University compared human melanoma cells that responded to the drugs against cells that did not.

The cells that did not respond to the drug contained higher levels of the protein SMURF2, according to the research published in the Journal of the National Cancer Institute.

But if the level of SMURF2 in the resistant melanoma cancer cells was artificially reduced, then the tumour cells became 100 times more sensitive to the drug.

Further analysis showed that removing SMURF2 lowers the level of a second protein, called MITF, in tumour cells. The research indicates that MITF is responsible for resistance to MEK inhibitors, at least in some cases.

"We're very excited about the potential for this new approach that has proved to be so effective in our experiments," Dr Wellbrock said.

Melanoma is one of the most deadly forms of cancer and is the fifth most common cancer in the UK.

"By the time many people are diagnosed with melanoma the cancer has already started to spread and advanced tumours can be highly resistant to conventional cancer treatments," Dr Wellbrock said.

"The development of resistance to new drugs has also been a major drawback."

"If we can identify more potent and less toxic drug combinations to tackle melanoma then we could save thousands of lives."

Cancer Research UK co-funded the research. Dr Julie Sharp from the charity said such efforts will form a key part of plans for the new Manchester Cancer Research Centre.

The centre is intended to bring together all the latest research developments and expertise to help revolutionise the way cancer is treated.

"Recently there have been some really exciting developments in treating melanoma - but new approaches that tackle the problem of resistance are still needed," she added.

Dr Wellbrock's team at Manchester University next task is to find a drug that can reduce the activity of SMURF2 in cancer cells.

Researchers are currently searching through existing drug collections for one that may already be approved for treating a different condition.

Copyright Press Association 2012

References

  • Smith M.P. et al. Effect of SMURF2 Targeting on Susceptibility to MEK Inhibitors in Melanoma, JNCI Journal of the National Cancer Institute, DOI: