Circadian Influences on Chemotherapy Efficacy in a Mouse Model of Brain Metastases of Breast Cancer.

ABSTRACT: Chemotherapy is more effective in the treatment of peripheral tumors than brain metastases, likely reflecting the reduced ability of chemotherapy to cross the blood-brain barrier (BBB) and blood-tumor barrier at efficacious concentrations. Recent studies demonstrate circadian regulation of the BBB. Thus, we predicted that optimally timed chemotherapy would increase anti-tumor efficacy in a model of brain metastases of breast cancer (BMBC). First, we characterized novel daily alterations in BBB permeability to a commonly used chemotherapeutic, ¹⁴C-paclitaxel, within BMBC following injections given at four time points across the day. Peak and trough ¹⁴C-paclitaxel concentrations within BMBC occurred during the mid-dark phase and at the beginning of the light phase, resp

SUBMITTER: Walker WH 

PROVIDER: S-EPMC8695439 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature