The presently disclosed subject matter relates to the administration of a KMT2D inhibitor for the treatment of a cancer. The present invention is based on the discovery that upon PI3K inhibition, KMT2D activity is upregulated, resulting in an increase in the expression of genes involved in breast cancer cell proliferation and tumor growth. Accordingly, the present invention provides methods for treating a subject that has cancer by administering a therapeutically effective amount of an KMT2D inhibitor.