Disclosed are methods for treating a subject with an EGFR dependent pathology. The method comprises the step of administering to the subject an effective amount of an agent (“First Agent”) that decreases the biological activity of iRhom1 and an effective amount of an agent (“Second Agent”) that decreases the biological activity of iRhom2. Alternatively, the method comprises the step of administering to the subject an effective amount of an agent (“First Agent”) that modulates formation of a complex between iRhom 1 and TACE and an effective amount of an agent (“Second Agent”) that modulates formation of a complex between TACE and iRhom2. Also disclosed are assays for identifying such agents.