A method for treating cancer comprising inhibiting transglutaminase activity is provided. Suitable cancer types for which the methods of the present disclosure can be used to treat include, but are not limited to, pancreatic, breast, and ovarian cancers and melanoma. The inhibition of transglutaminase activity may be performed by one or more techniques, including, but not limited to, downregulating transglutaminase expression, inhibiting TG2 translation, or blocking TG2 enzymatic activity, such as with a small molecule inhibitor or intracellular antibody (intrabody).