# Use SLFN11 status to decide which antibody-drug payload to give next

Source: https://onco.cc/ideas/idea-bio1-slfn11-payload-guidance/  
OnCo record `idea-bio1-slfn11-payload-guidance` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A single protein predicts whether a tumour will respond to DNA-damaging drug payloads. Measuring it could stop patients receiving a second drug of the same kind that will not work.

## Summary

SLFN11 expression predicts sensitivity to topoisomerase 1 inhibitors and platinum across preclinical models and some clinical series, and its loss is a recognised mechanism of payload resistance. With most current ADCs carrying topoisomerase 1 payloads, SLFN11 immunohistochemistry on a progression biopsy could distinguish antigen-driven from payload-driven failure and direct patients to a different payload class such as a tubulin inhibitor.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: SLFN11 loss at progression identifies payload-class resistance and predicts failure of a second topoisomerase-payload ADC, while SLFN11-retained tumours can benefit from an antigen switch within the same payload class.
- Rationale: SLFN11 status provides the missing test that turns payload-class switching from a rule of thumb into a biomarker-directed decision; the assay is a standard immunohistochemistry stain.
- Proposed test: Retrospective SLFN11 staining of progression biopsies from patients who received sequential ADCs, correlating with response to the second agent; prospective validation in a sequencing trial.
- Maturity: preclinical-evidence
- Actor: research

## 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/), [Sequencing HER2 ADCs by payload after T-DXd](https://onco.cc/ideas/idea-her2-adc-sequencing-payload/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/), [Payload (ADC)](https://onco.cc/terms/payload/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/)

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