Provided herein are compositions for reducing CLPTM1L expression in a cell as well as methods for using such compositions to treat or prevent cancer in a subject. In particular, compositions comprising RNAi-inducing constructs targeted to CLPTM1L and methods of administering such compositions to a subject to treat or prevent a disease or condition associated with CLPTM1L over-expression (e.g., lung cancer) are provided herein.