# CNS penetration (brain-penetrant drugs)

Source: https://onco.cc/terms/cns-penetration/  
OnCo record `cns-penetration` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier
- Wikipedia: https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier

## Connected records

- terms: [Brain metastases (intracranial disease)](https://onco.cc/terms/brain-metastases/), [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/), [Intrathecal therapy (lumbar puncture, Ommaya reservoir)](https://onco.cc/terms/intrathecal-therapy/), [Leptomeningeal disease](https://onco.cc/terms/leptomeningeal-disease/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- drugs: [Osimertinib](https://onco.cc/drugs/osimertinib/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Tucatinib](https://onco.cc/drugs/tucatinib/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/)

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