Cross-resistance
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.
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.
Pages like this
not linked directly; found by shared links- TermRefractory
Shares Lines of therapy, Drug resistance (primary and acquired).
- TermRelapsed / refractory (R/R)
Shares Lines of therapy, Drug resistance (primary and acquired).
- CompanyMersana Therapeutics
- IdeaUse SLFN11 status to decide which antibody-drug payload to give next
- IdeaSequencing HER2 ADCs by payload after T-DXd
- TermExatecan (and derivatives)
- TermProgression
Shares Lines of therapy, Drug resistance (primary and acquired).
- IdeaSequential multiple-assignment randomised trials to find the best order of ADCs