{"entity":{"id":"idea-bio1-antigen-mapping-at-progression","kind":"idea","name":"Re-map the tumour's surface proteins before choosing the next antibody drug","aka":[],"tldr":"Antibody drugs need their target to still be present. After one fails, checking which surface markers remain would guide the choice of the next one instead of guessing.","summary":"Antigen loss and downregulation are documented mechanisms of ADC, bispecific and CAR-T failure. A standardised multiplex panel measuring the main clinical antigens (HER2, TROP2, HER3, CEACAM5, B7-H3, Nectin-4, FOLR1 and others) on a progression biopsy, or by immuno-PET where available, would let clinicians select the next agent by present antigen rather than by tumour type convention.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":["idea-payload-switching"],"cancers":[],"sections":[],"technologies":["adc","histopathology-ihc","immuno-pet","single-cell-spatial"],"targets":["her2","trop2","her3","ceacam5","b7h3","folr1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity"],"keyPapers":["paper-slamon-her2-breast-ovarian-science-1989","paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Antigen-guided selection of the next antibody-based agent after progression yields a higher response rate than conventional selection, and antigen loss explains a substantial fraction of failures on the prior agent.","rationale":"Antigen expression is dynamic under treatment pressure and archival tissue is a poor guide; the panel technology is routine immunohistochemistry or multiplex imaging, so this is a logistics rather than discovery problem.","test":"Prospective cohort of 200 patients progressing on an ADC: run the panel, record whether the recommendation differs from the clinician's plan, and compare outcomes where it was followed.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-antigen-mapping-at-progression/","neighbours":{"idea":[{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"target":[{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"ceacam5","kind":"target","name":"CEACAM5","route":"/targets/ceacam5/"},{"id":"folr1","kind":"target","name":"Folate receptor alpha","route":"/targets/folr1/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"},{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"paper":[{"id":"paper-slamon-her2-breast-ovarian-science-1989","kind":"paper","name":"Slamon 1989: HER2/neu in human breast and ovarian cancer","route":"/key-papers/paper-slamon-her2-breast-ovarian-science-1989/"},{"id":"paper-yarden-sliwkowski-erbb-network-nrmcb-2001","kind":"paper","name":"Yarden and Sliwkowski 2001: untangling the ErbB signalling network","route":"/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/"}]}}