Overactive epidermal growth factor receptor (EGFR) signaling has been linked to the development of cancer. Several drug therapies have been developed to treat these EGFR-associated cancers; however, many patients have developed resistance to these drugs and are therefore no longer responsive to drug treatment. In a recent research article published in the Journal of Clinical Investigation , Goutham Narla and colleagues at Case Western Reserve University sought to better understand the molecular players in the EGFR signaling pathway in hopes of finding new drug targets for EGFR-associated cancers. Using cancerous human lung tissue and a mouse model of EGFR-associated lung cancer, The Narla team discovered that two tumor suppressor genes, KLF6 and FOXO1, function to disrupt overactive EGFR signaling. After treating the cancerous lung tissue and cancer-prone mice with an FDA-approved drug called trifluoperazine hydrochloride (TFP), which increases the activity of FOXO1, they restored the effectiveness of the anti-EGFR drug erlotinib and reduced tumor growth. Their work identified new drug targets for EGFR-associated cancers and suggests that combinatorial drug therapy regimens may improve treatment outcome.
TITLE:
Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response
AUTHOR CONTACT:
Goutham Narla
Case Western Reserve University and University Hospitals, Cleveland, OH, USA
Phone: 347-255-0885; E-mail: Goutham.Narla@mssm.edu
View this article at: http://www.jci.org/articles/view/62058?key=9eb9f31baf7df0c3365e
Journal of Clinical Investigation