Merlin marks activity for GlaxoSmithKline drug in mesothelioma

The lack of a tumor suppressor gene known as NF2 could tag those patients most likely to respond to an investigational mesothelioma drug, according to a clinical study funded by GlaxoSmithKline ($GSK).

Mesothelioma is a rare form of cancer normally caused by exposure to asbestos, and it progresses quickly, with most patients dying only 9-17 months after diagnosis. Around half of mesothelioma patients have an inactivated form of the NF2 gene. This gene codes for a protein called merlin, which in turn regulates the protein focal adhesion kinase (FAK). People with an inactivated form of NF2 have higher levels of FAK, which means their cancers are more invasive and more likely to spread.

The oral drug code-named GSK2256098 inhibits FAK, and in a Phase I trial that included 29 patients with mesothelioma, it slowed the progression of disease more in patients with higher levels of the merlin protein. These results were presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin.

"These findings are important but preliminary," said Jean-Charles Soria of South Paris University in a statement. "They show that merlin is a potential biomarker in mesothelioma that may enable us to identify a subset of patients who could benefit from GSK2256098 and have longer, progression-free survival. Mesothelioma is a deadly disease without many treatment options, and therefore identification of novel and effective therapies is needed."

Merlin could also have potential as a marker in melanoma, or in the central nervous system tumor meningioma. However, these are still very early results, so more and larger clinical trials will be needed before it could be used as a prognostic marker or as a route to new treatments.

- read the press release