Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint activator, which is preferably .beta.-lapachone, or a derivative or analog thereof, combined with an oncogenic kinase modulator, preferably imatinib. This combination of the cell cycle checkpoint activator with the oncogenic kinase modulator results in an unexpectedly greater than additive (i.e., synergistic) apoptosis in cancer cells. The invention includes methods of treating cancers by administering the combination of the cell cycle checkpoint activator and the oncogenic kinase modulator, pharmaceutical compositions comprising the combination of drugs used in these methods, as well as pharmaceutical kits.