The present disclosure relates generally to compositions and methods of treating cancers, such as glioblastoma and non-Hodgkins lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising the administration of a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination therapy can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared to the administration of either the BET inhibitor or the chemotherapeutic agent alone.