{"entity":{"id":"cns-penetration","kind":"term","name":"CNS penetration (brain-penetrant drugs)","aka":["CNS penetration","CNS-penetrant","CNS penetrant","brain-penetrant","brain penetrant","brain penetration","blood-brain barrier penetration","BBB-penetrant","CNS-active","intracranial efficacy","CNS efficacy","CNS progression","CNS protection","CSF concentration","Kp,uu","efflux transporter","P-glycoprotein substrate","efflux transporters"],"tldr":"How well a drug crosses from the blood into the brain, where most cancer drugs are kept out by the blood-brain barrier. Brain-penetrant pills can treat and prevent brain metastases; those that are not leave the brain as a sanctuary where the cancer regrows.","summary":"Third-generation EGFR (osimertinib) and ALK (alectinib, lorlatinib) inhibitors were designed for CNS penetration and cut brain progression dramatically compared with earlier drugs; tucatinib, and unexpectedly T-DXd, are active against HER2-positive brain metastases; temozolomide, lomustine and vorasidenib are brain-penetrant by design. Penetration is measured as unbound brain-to-plasma ratio (Kp,uu) or CSF concentration and is limited by efflux pumps (P-glycoprotein, BCRP). Intracranial response rates and CNS progression-free survival are now standard secondary endpoints in lung and breast cancer trials, and intrathecal or intraventricular delivery bypasses the barrier for leptomeningeal disease.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier"}],"tags":[],"related":["brain-metastases","leptomeningeal-disease","intrathecal-therapy","tki-term"],"cancers":[],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["osimertinib","tucatinib","trastuzumab-deruxtecan","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},"route":"/terms/cns-penetration/","neighbours":{"term":[{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"lymphoma-tx-cns-prophylaxis","kind":"term","name":"CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it","route":"/terms/lymphoma-tx-cns-prophylaxis/"},{"id":"intrathecal-therapy","kind":"term","name":"Intrathecal therapy (lumbar puncture, Ommaya reservoir)","route":"/terms/intrathecal-therapy/"},{"id":"leptomeningeal-disease","kind":"term","name":"Leptomeningeal disease","route":"/terms/leptomeningeal-disease/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"drug":[{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"},{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"}]}}