{"entity":{"id":"idea-bio1-slfn11-payload-guidance","kind":"idea","name":"Use SLFN11 status to decide which antibody-drug payload to give next","aka":[],"tldr":"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.","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","idea-her2-adc-sequencing-payload"],"cancers":[],"sections":[],"technologies":["adc","histopathology-ihc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["payload","adc-sequencing"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"small","horizonYears":3},"route":"/ideas/idea-bio1-slfn11-payload-guidance/","neighbours":{"idea":[{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","route":"/ideas/idea-payload-switching/"},{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","route":"/ideas/idea-her2-adc-sequencing-payload/"}],"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":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"},{"id":"payload","kind":"term","name":"Payload (ADC)","route":"/terms/payload/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}]}}