Targeting Mesothelioma Cancer Stem Cells

(Stem Cells News image)

Verastem Inc, focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, announced that a paper, entitled “Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship,” has been published by Verastem scientists in the latest issue of the journal Science Translational Medicine.

The paper describes the finding that loss of the tumor suppressor merlin predicts for increased responsiveness to drugs targeting cancer stem cells through inhibition of focal adhesion kinase (FAK). Since merlin loss is particularly prevalent in mesothelioma (approximately 50% of patients), the efficacy of FAK inhibition was demonstrated in several cellular and in vivo mesothelioma models.

The publication further describes the strong tumor-initiating capability of mesothelioma cancer stem cells and the observation that the standard of care agents pemetrexed and cisplatin augment cancer stem cells. In contrast, FAK inhibition effectively reduces cancer stem cells in preclinical models of mesothelioma.

“These data demonstrate that FAK inhibition is particularly effective in models of merlin-negative mesothelioma,” said Jonathan Pachter, Ph.D., Verastem Head of Research.

“These results build upon key findings published earlier this year by our collaborators at Fox Chase Cancer Center which demonstrated that merlin loss drives the development of highly aggressive malignant mesothelioma which is enriched for cancer stem cells.

Accordingly, in a merlin-negative mesothelioma patient-derived tumor model, FAK inhibitor treatment as maintenance therapy prolonged the inhibition of tumor growth following treatment with pemetrexed and cisplatin.”


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