New Drug Slows the Progression of Mesothelioma

 By Warren Miller.    12th October 2013

A new drug has been recently trialed that may slow down the spread of mesothelioma in patients who have a genetic abnormality.

NF2 gene merlin activity

Preliminary findings have demonstrated this in patients lacking an active tumour suppressor gene called NF2.

In about half of mesothelioma patients this gene has not been activate. The NF2 gene produces a protein called Merlin which in turn regulates another protein called Focal Adhesion Kinase (FAK) in mesothelioma.

So, when the gene and protein are inactive, the activity of the FAK protein is increased and mesothelioma cells start to spread. When the NF2 gene and Merlin activity is restored, FAK activity and mesothelioma cell invasion are decreased.

GSK2256098 Drug Trial

A recent study suggested that the spread of mesothelioma could be stopped by inhibiting the FAK protein. So a new drug, currently called GSK2256098, was developed. The drug was given to 29 mesothelioma patients in the UK, France and Australia from 2010.

The drug was taken orally, twice a day with doses ranging from 300mg to 500 mg, most taking 1000 mg a day.
The results were that on average it took more than 4 months for the mesothelioma to progress:

  • 14 patients had stable disease
  • Mesothelioma progressed in 9 patients
  • 3 had non-measurable disease
  • 3 left the study before their progress could be evaluated

However, in mesothelioma patients where merlin was inactivated, the average time before the disease progressed was around 6 months, compared to 11 weeks in patients with active merlin and nearly 11 weeks in patients in whom the activity of merlin was unknown. The side effects of the GSK2256098 drug were noted to be tolerable and low grade.

The findings are only preliminary, but they show that Merlin is a potential biomarker in mesothelioma and may lead to novel targets of treatment. Given that many mesothelioma patients do not live longer than 12 months after diagnosis, the finding is encouraging.

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