The small survival protein survivin is overexpressed in head and neck tumours and promotes the survival of malignant cells. This contributes to increased resistance to chemotherapy and radiotherapy and worsens the prognosis for affected patients. Due to its central role in tumor progression, survivin is considered a promising therapeutic target, but it is difficult to attack with small chemical molecules, especially in a clinical context. 
Since survivin mediates its cellular functions primarily via protein-protein interactions, effective inhibitors must be able to efficiently block relevant surface areas. One promising strategy is the use of antibodies – in particular, high-affinity, single-chain nanobodies, which open up innovative biomedical possibilities due to their small size and high specificity. 

The scientists have developed nanobodies (SuN) in alpacas that target survivin, specifically disrupting critical protein interactions and thus impairing the function of survivin. These nanobodies will now be coupled with tumour-specific PROTACs (proteolysis-targeting chimeras) that specifically recruit the cellular E3 ubiquitin ligase Pirh2, an enzyme that is also overexpressed in head and neck tumors. Through the use of SuN-PROTACs, survivin in Pirh2-positive head and neck tumor cells can be specifically degraded via the cellular proteasome. This could break through the resistance mechanisms of the tumour cells and restore their sensitivity to established cancer therapies.