{"entity":{"id":"idea-bio1-lytac-surface-degraders","kind":"idea","name":"Drag cancer's surface and secreted proteins to the cell's recycling bin","aka":[],"tldr":"Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be broken down.","summary":"Lysosome-targeting chimeras (LYTACs) and antibody-based equivalents (KineTACs) use receptors such as the cation-independent mannose-6-phosphate receptor or ASGPR to internalise and degrade extracellular and membrane proteins. Cancer targets that resist antibody blockade because they are shed, recycled or in excess (for example growth factors, immunosuppressive ligands, and non-internalising surface antigens) become tractable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-tme-immunosuppression"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"LYTAC-mediated removal of a shed immunosuppressive ligand from the tumour microenvironment restores T-cell infiltration and improves checkpoint inhibitor efficacy in a syngeneic model more than a blocking antibody alone.","rationale":"Degradation removes protein rather than occupying it, which matters where ligand is continuously produced. The chemistry has been demonstrated for several model targets in cells and mice.","test":"Build a LYTAC against one shed ligand with established immunosuppressive function, compare with a blocking antibody in matched syngeneic tumours, and measure ligand levels and T-cell infiltration.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},"route":"/ideas/idea-bio1-lytac-surface-degraders/","neighbours":{"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"institution":[{"id":"stanford","kind":"institution","name":"Stanford Health Care / Stanford Cancer Institute","route":"/institutions/stanford/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}