It is disclosed herein that suppressive ODNs are of use for preventing or delaying the formation of a tumor, reducing the risk of developing a tumor, treating a tumor, preventing conversion of a benign to a malignant lesion, or preventing metastasis. In some embodiments, methods are disclosed herein for treating, preventing or reducing the risk of developing a tumor, such as esophageal, gastrointestinal, liver, lung, skin and colon tumors or a mesothelioma. Generally, the methods disclosed herein include selecting a subject for treatment and administering to the subject a therapeutically effective amount of one or more suppressive ODN. In some examples, additional agents can also be administered to the subject of interest.