CNS penetration (brain-penetrant drugs)
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.
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.
Pages like this
not linked directly; found by shared links- TermProphylactic cranial irradiation (PCI)
Shares Intrathecal therapy (lumbar puncture, Ommaya reservoir), Brain metastases (intracranial disease).
- TermWhole-brain radiotherapy (WBRT)
Shares Leptomeningeal disease, Brain metastases (intracranial disease).
- IdeaBrain metastases included by default in every solid-tumour trial
Shares Tucatinib, Osimertinib, Trastuzumab deruxtecan.
- TermRash and skin toxicity (acneiform rash, paronychia)
- IdeaSystemic-first management of HER2-positive brain metastases
Shares Tucatinib, Trastuzumab deruxtecan.
- TermQT prolongation
- IdeaTreat brain metastases as a disease with its own trials programme
Shares Tucatinib, Osimertinib.
- TermOn-target resistance mutations (gatekeeper, solvent-front, compound)