Provided are methods and compositions for enhancing radiotherapy in various cancers by administering
dopamine receptor (DRD2)‐binding
phenylpiperazine derivatives such as
brexpiprazole,
cariprazine, pipamperone, and perospirone.
In vitro studies show that combining these agents with
ionizing radiation (e.g., 5 Gy) significantly reduces
cancer cell survival, suppresses metastatic and stemness markers (e.g., CD44, MMP‑2,
Snail, Nanog), and promotes
apoptosis. Fractionated or single‐fraction
radiation regimens can be paired with DRD2 antagonists to lower treatment‐resistant phenotypes, decrease the likelihood of recurrence, and potentially reduce necessary
radiation dosages. The approach applies to breast,
prostate,
lung, pancreatic, and
brain cancers, among others. Depending on tumor characteristics, additional chemotherapeutic or immunotherapeutic agents may further improve outcomes.