Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.

What was studied

This paper tested a drug that blocks the enzyme peroxiredoxin 3 (PRX3) in mesothelioma. The compound is thiostrepton (TS). It was tested in cells and in a phase 1 trial. The patients had relapsed pleural mesothelioma. They also had malignant pleural effusion. The drug product RSO-021 was given into the pleura each week at 90 mg. The trial is NCT05278975.

What they found

Deleting the PRX3 gene harmed mitochondria and slowed mesothelioma growth. TS caused cell death in patient-derived mesothelioma samples. In the trial, RSO-021 at 90 mg was well tolerated. The disease control rate at 12 weeks was 67. Tumor reductions were also seen. The trial met its main aims of safety, tolerability and dose finding. Genomic screening found SLC7A11 as a mediator of resistance to TS.

What it means for patients

The authors say RSO-021 was well tolerated and led to disease control. They say it was linked to tumor reductions. They suggest that combined targeting may further boost its effect.

Why it is not certain yet

Secondary endpoints are still being explored. These include response rate and progression free survival. The abstract does not give the number of patients. A phase 1 trial mainly checks safety and dose.

Source

Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.

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