{"entity":{"id":"cross-resistance","kind":"term","name":"Cross-resistance","aka":["cross-resistant","cross resistance","payload cross-resistance","cross-reactive resistance","collateral sensitivity","optimal sequencing"],"tldr":"When a cancer that has become resistant to one drug is also resistant to another it has never seen, because the two share a mechanism. It is the central worry in deciding the order (sequencing) of similar drugs.","summary":"Two ADCs carrying topoisomerase-I payloads (T-DXd, sacituzumab govitecan, datopotamab deruxtecan) may fail one after another because resistance is to the payload, not the antibody; ARPIs show near-complete cross-resistance in prostate cancer; second-generation ALK or BTK inhibitors overcome some but not all resistance to the first. Cross-resistance data usually come from retrospective series, which is why 'optimal sequencing' remains unresolved in HR-positive breast, HER2-positive breast, prostate and CLL, and why some trials test switching mechanisms (payload class, target) rather than drugs of the same class. The opposite, collateral sensitivity, is when resistance to one drug creates vulnerability to another.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Cross-resistance","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cross-resistance"}],"tags":[],"related":["adc-sequencing","resistance","rechallenge","first-line"],"cancers":[],"sections":["adcs","targeted-therapy"],"technologies":["adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},"route":"/terms/cross-resistance/","neighbours":{"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"first-line","kind":"term","name":"Lines of therapy","route":"/terms/first-line/"},{"id":"rechallenge","kind":"term","name":"Rechallenge and retreatment","route":"/terms/rechallenge/"}],"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"cancer":[{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"paper":[{"id":"paper-gainor-alk-resistance-mutations-cancer-discov-2016","kind":"paper","name":"Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer","route":"/key-papers/paper-gainor-alk-resistance-mutations-cancer-discov-2016/"},{"id":"paper-shaw-alk-l1198f-resensitisation-nejm-2016","kind":"paper","name":"Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F","route":"/key-papers/paper-shaw-alk-l1198f-resensitisation-nejm-2016/"}],"biomarker":[{"id":"alk-resistance-mutation","kind":"biomarker","name":"ALK kinase-domain resistance mutation (G1202R and the rest)","route":"/biomarkers/alk-resistance-mutation/"},{"id":"ar-ligand-binding-domain-mutation","kind":"biomarker","name":"AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)","route":"/biomarkers/ar-ligand-binding-domain-mutation/"},{"id":"btk-c481s","kind":"biomarker","name":"BTK resistance mutations: C481S, and L528W and T474I after the non-covalent inhibitors","route":"/biomarkers/btk-c481s/"}]}}