A cancer gene therapy involves the expression of a foreign gene in cancer cells. However, the current methods to control the transgene expression are imperfect, with leaky expression usually found in normal cells. This leakiness can lead to harmful side effects in patients, especially if the transgene encodes a toxic protein. Herein, my studies aim to invent, as well as improve upon regulatory tools to control transgene expression in cancer gene therapies. Compared to the traditional promoter-based or cell surface marker-based approaches, my approach targets an intracellular protein defect caused by several mutations that are prevalent in cancers. Additionally, I improved the inducible gene expression system, further eliminating its background leakiness. Together, my studies offer novel cell-specific targeting and temporal control options, expanding the current gene therapy toolbox.