To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy.

ABSTRACT: Toxicity and emerging drug resistance pose important challenges in poly-adenosine ribose polymerase inhibitor (PARPi) maintenance therapy of ovarian cancer. We propose that adaptive therapy, which dynamically reduces treatment based on the tumor dynamics, might alleviate both issues. Utilizing in vitro time-lapse microscopy and stepwise model selection, we calibrate and validate a differential equation mathematical model, which we leverage to test different plausible adaptive treatment schedules. Our model indicates that adjusting the dosage, rather than skipping treatments, is more effective at reducing drug use while maintaining efficacy due to a delay in cell kill and a diminishing dose-response relationship. In vivo pilot experiments confirm this conclusion. Although our focus is toxic

SUBMITTER: Strobl MAR 

PROVIDER: S-EPMC11190943 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature