The Convergence of Tumor-Specific Promoters and Nanodelivery Systems in Precision Cancer Gene Therapy

Gene therapy is an emerging approach for treating cancer by delivering therapeutic nucleic acids into malignant cells. However, tumor heterogeneity and the tumor microenvironment (TME) undermine the effectiveness of conventional gene therapy, which may lead to off-target activity in normal cells and limit therapeutic efficacy. Tumor-specific promoters (TSPs) provide transcription-level control by activating expression mainly in malignant cells through oncogenic signaling pathways or tumor-associated conditions such as hypoxia and inflammation. Recent work has demonstrated that gene therapy combined with suitable nanodelivery systems, including lipid-based, polymeric and inorganic systems, enables more precise tumor-restricted expression and enhanced antitumor effects. This review summarizes the current landscape of TSP discovery and engineering, and discusses considerations for their integration into emerging nanodelivery systems for cancer treatment.