As reported by Rebouissou and colleagues in Science Translational Medicine, a subset of muscle-invasive bladder cancers that present with a basal-like phenotype is associated with poorer survival, EGFR pathway activation, and sensitivity to EGFR inhibition.
Assessment of data from 383 tumors revealed that 23.5% displayed a basal-like phenotype characterized by expression of epithelial basal cell markers and shorter survival. These basal-like tumors exhibited activation of the EGFR pathway associated with frequent EGFR gains and activation of an EGFR autocrine loop. The tumor cells were found to be sensitive to anti-EGFR therapy using both a 40-gene expression classifier derived from human tumors to identify bladder cancer cell lines and a mouse model of chemically induced bladder cancer corresponding to human basal-like bladder cancer.
The authors concluded, “Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive [muscle-invasive bladder cancer] tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.” ■
Rebouissou S, et al: Sci Transl Med 6:244ra91, 2014.