Abstract: The described invention provides a method of treating a patient with an epithelial cancer comprising administering a composition comprising a therapeutic amount of an inhibitor of a BTK protein and one or more chemotherapeutic agent(s) selected from the group consisting of an antimetabolite, a platinum coordination compound, an alkylating agent and a combination thereof, wherein the composition is effective to reduce one or more of tumor cell growth, tumor cell clonogenicity, tumor cell proliferation, tumor cell viability and tumor volume and the therapeutic amount of the inhibitor of a BTK protein and the one or more chemotherapeutic agent(s) exerts a synergistic effect. The described invention also provides methods of treating a chemotherapy drug-resistant cancer and sensitizing a cancer patient to chemotherapy.