# Re-map the tumour's surface proteins before choosing the next antibody drug

Source: https://onco.cc/ideas/idea-bio1-antigen-mapping-at-progression/  
OnCo record `idea-bio1-antigen-mapping-at-progression` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- ideas: [Payload-class switching as the rule for ADC sequencing](https://onco.cc/ideas/idea-payload-switching/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Immuno-PET](https://onco.cc/technologies/immuno-pet/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- targets: [B7-H3](https://onco.cc/targets/b7h3/), [CEACAM5](https://onco.cc/targets/ceacam5/), [Folate receptor alpha](https://onco.cc/targets/folr1/), [HER2](https://onco.cc/targets/her2/), [HER3](https://onco.cc/targets/her3/), [TROP2](https://onco.cc/targets/trop2/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- key papers: [Slamon 1989: HER2/neu in human breast and ovarian cancer](https://onco.cc/key-papers/paper-slamon-her2-breast-ovarian-science-1989/), [Yarden and Sliwkowski 2001: untangling the ErbB signalling network](https://onco.cc/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/)

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