Targeted gene delivery by free-tissue transfer in oncoplastic reconstruction

Surgery is the most effective curative treatment for various tumour types. Despite a current preference for conservative surgery, radical excision retains a clearly defined role in modern management of locoregional disease. Extirpative defects are reconstructed routinely using free-tissue transfer from a distant donor site. Although these free flaps currently provide no direct therapeutic benefit, advances in gene-delivery techniques offer the possibility to genetically modify flaps to produce potent targeted treatments with greater anatomical control. Several promising therapeutic strategies, including virus-directed enzyme prodrug therapy, genetic radionuclide therapy, and free-flap radioprotection, have the potential to extend the role of the free flap beyond its immediate goal of restoring form and function to patients, but challenges exist. Work to translate therapeutic free-tissue transfer from preclinical study to clinical use is in progress.