Provided herein are methods for a novel combination therapy for treating a glutamine-addicted cancer in a subject in need thereof, which comprises the administration of a glutaminase antagonist and a pro-apoptotic compound. Specific glutaminase antagonists and pro-apoptotic compounds are provided. In some embodiments, the glutaminase antagonist is 6-diazo-5-oxo-1-norleucine (DON) and the pro-apoptotic compound is a Bcl-2 family member antagonist. In some embodiments, the pro-apoptotic compound is obatoclax mesylate, navitoclax, or fenretinide. In some embodiments, the glutamine-addicted cancer is a cancer in which Myc is deregulated. In some embodiments, the cancer is a pediatric cancer.
