本期配图来自2024年4月15日发表在Experimental Hematology & Oncology（IF=10.9）上的文章《A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases》
- The anti-HER2 Fab can penetrate deeper brain parenchyma, which should be explained by its smaller size.
- Fab may spread through the lymphatic system to the interstitium of the brain and subsequently eliminate in the venous circulation.
- Fab will be able to bind to HER2-overexpressing HER2 receptors in brain metastases, inhibiting its effects.
- After intraventricular administration in rats, it was observed that the cerebral blood outflow of Fab was 10 times lower than that of trastuzumab and the cerebral permeability was 2 times higher.
conclusion
Fab can significantly reduce cerebral efflux to the bloodstream after cerebrospinal fluid injection and enhance brain penetration, so it may be a new and effective drug for the treatment of HER2 breast cancer brain metastasis, which will be demonstrated by a phase I clinical trial.
Background supplements
Despite two decades of significant therapeutic advances, brain metastases remain the leading cause of death in women with metastatic HER2 breast cancer. One of these limitations is the limited passage of drugs to the blood-brain barrier after intravenous administration, and the large outflow of drugs, including monoclonal antibodies, into the cerebrospinal fluid after administration.
Bibliography:
Angeli E, Paris J, Le Tilly O, Desvignes C, Gapihan G, Boquet D, Pamoukdjian F, Hamdan D, Rigal M, Poirier F, Lutomski D, Azibani F, Mebazaa A, Herbet A, Mabondzo A, Falgarone G, Janin A, Paintaud G, Bousquet G. A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases. Exp Hematol Oncol. 2024 Apr 15; 13(1):41. doi: 10.1186/s40164-024-00513-7. PMID: 38622749; PMCID: PMC11017592.
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