Compositions and methods for regulating EGFR amplification in cancer cells for improving efficacy of EGFR-targeted anti-cancer agents

A method for treating a subject having EGFR inhibitor (EGFRi) resistant tumors, comprising;

• a) contacting a tumor comprising altered EGFR copy numbers with an agent that modulates amplification of EGFR to a level which sensitizes cells in said tumor to EGFR inhibitors;
• and
• b) administering to said subject an EGFRi, thereby reducing tumor cell proliferation or inducing tumor cell killing which exceeds that observed in tumor cells not treated with the agent of step a)
• wherein the modulation of EGFR reduces EGFR copy number heterogeneity.