Topoisomerase-I inhibitor payloads
Topoisomerase-I inhibitor payloads are the payload class behind Enhertu, Trodelvy and Dato-DXd: poisons that trap the enzyme that untwists DNA, so dividing cells break their own DNA.
Camptothecin derivatives (SN-38, DXd, exatecan and its children, T030) stabilise topoisomerase I on DNA. They are membrane permeable, so most give a bystander effect, and they tolerate high drug-to-antibody ratios. The class shares resistance routes: TOP1 mutations, loss of SLFN11 and efflux pumps, which is why a second topoisomerase-I ADC after the first fails is often disappointing. Interstitial lung disease, neutropenia and diarrhoea are class toxicities that differ in weight between members.
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not linked directly; found by shared links- PathwayDrug efflux pumps (ABC transporters)
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