Provided herein are methods of treating cancers expressing specific biomarkers with HER3 and/or EGFR inhibitors, and provided herein are also biomarkers and uses thereof in determining likelihood of effective cancer treatment with HER3 and/or EGFR inhibitors. In one aspect, the disclosure provides methods for treating a cancer, comprising administering to a patient diagnosed with said cancer a therapeutically effective amount of a HER3 inhibitor, an EGFR inhibitor, or a combination of a HER3 inhibitor and an EGFR inhibitor. Also disclosed herein are kits comprising components for performing the methods for determining whether a patient diagnosed with cancer is indicated as likely to be responsive to treatment with a HER3 inhibitor and/or an EGFR inhibitor.