Hypothesis
A long-circulating liposomal doxorubicin would keep the drug available to the tumour long enough, after microbubble-mediated focused ultrasound opened the blood-brain barrier, to extend survival where a single dose of free doxorubicin had not.
What failed
In orthotopic HSJD-DIPG-07 xenografts, histology 24 hours after treatment showed liposome extravasation in healthy controls but not in the tumour-bearing animals; bioluminescence signal did not fall after treatment, and survival did not differ significantly between treated and control animals (p = 0.3) for free doxorubicin or either liposomal formulation.
Broken assumption
An ultrasound-opened blood-brain barrier lets circulating liposomal drug into the tumour.
Why
The authors report no treatment effect from any formulation combined with ultrasound, with the histology indicating the liposomes did not reach the tumour.
From the published paper: Haumann et al. Translational Medicine Communications, 2022. ↗CC BY