Early disease progression in a phase I study of bortezomib (B), cetuximab (C), and intensity-modulated radiation therapy (IMRT) for squamous cell carcinoma of the head and neck (SCCHN).

Targeting NF-κB in Mouse Models of Lung Adenocarcinoma

“…Supporting this, combination of bortezomib with either JNK or STAT3 inhibitors was shown to overcome bortezomib resistance (8,9). Combination of bortezomib with EGFR inhibition upstream of these pathways also enhanced activity in preclinical studies, but when combined with radiation in a phase I trial, was unexpectedly associated with early disease progression (10). Antagonism of radiation-induced EGFR degradation with co-activation of NF-κB and these other prosurvival pathways was observed, providing a cautionary tale about the limits of extrapolation from experimental models.…”