Use SLFN11 status to decide which antibody-drug payload to give next
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.
SLFN11 expression predicts sensitivity to topoisomerase 1 inhibitors and platinum across many 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.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.
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not linked directly; found by shared links- IdeaSequential multiple-assignment randomised trials to find the best order of ADCs
Shares Sequencing HER2 ADCs by payload after T-DXd, Payload-class switching as the rule for ADC sequencing, ADC sequencing, Acquired resistance to every therapy.
- TermT030 (belotecan derivative)
Shares Payload (ADC), Topoisomerase-I inhibitors (and ADC payloads), Antibody-drug conjugate (ADC).
- TermExatecan (and derivatives)
Shares ADC sequencing, Payload (ADC), Topoisomerase-I inhibitors (and ADC payloads), Antibody-drug conjugate (ADC).
- IdeaRe-map the tumour's surface proteins before choosing the next antibody drug
Shares Payload-class switching as the rule for ADC sequencing, Histopathology & immunohistochemistry, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
- CompanyMersana Therapeutics
Shares ADC sequencing, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
- IdeaCombination baskets defined by resistance mechanism rather than by cancer type
Shares Payload-class switching as the rule for ADC sequencing, Acquired resistance to every therapy, Antibody-drug conjugate (ADC).
- IdeaRandomise the next line of treatment before the first one fails
Shares ADC sequencing, Acquired resistance to every therapy.
- Key paperDESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer
Shares Payload-class switching as the rule for ADC sequencing, ADC sequencing, Payload (ADC), Topoisomerase-I inhibitors (and ADC payloads).