The invention provides methods for treating various types of cancer/tumor by administering the combination of DII4 antagonists, in particular, DII4 antibodies and fragments thereof that specifically bind human DII4, and chemotherapeutic agents. Such combination therapies exhibit synergistic effects compared to the treatment with either agent alone. Thus, the methods of the invention are particularly beneficial for cancer patients who have low tolerance to the side effects caused by high dosages required for the treatment by either agent alone, by being able to reduce effective dosages. Pharmaceutical compositions and kits containing DII4 antagonists and chemotherapeutic agents are also provided.
