Rechallenge and retreatment
Giving a drug again after a break, on the theory that the cancer's resistance faded while it was off the drug. Sometimes it works: bowel cancers can respond again to EGFR antibodies once resistant clones have receded.
Anti-EGFR rechallenge in RAS wild-type colorectal cancer works when ctDNA shows RAS-mutant clones have declined (CHRONOS, CRICKET). Platinum rechallenge is standard for platinum-sensitive relapse in ovarian and small-cell lung cancer; BTK inhibitor or venetoclax retreatment after fixed-duration CLL therapy is effective; checkpoint inhibitor rechallenge after stopping for toxicity or after a treatment-free interval gives responses in a minority. Planned drug holidays (intermittent ADT, stop-and-go FOLFOX in OPTIMOX, adaptive therapy in prostate cancer) trade some disease control for toxicity relief and may slow resistance by preserving sensitive cells.