The study identified five genes potentially responsible for abiraterone resistance in castrate-resistant prostate cancer (CRPC) patients.
High expression of the PPP1CA gene, in particular, was linked to a poorer prognosis. Further investigation revealed that silencing PPP1CA increased the sensitivity of CRPC cells to abiraterone while also increasing apoptosis and inhibiting colony development. Conversely, overexpressing PPP1CA had the reverse effect. The researchers discovered that the natural substance nodularin-R could inhibit PPP1CA in a dose-dependent manner. Combining nodularin-R with abiraterone synergistically inhibited resistant CRPC cell activity.

In vivo studies also showed that the combination therapy significantly inhibited tumor growth and reduced inducible PPP1CA expression.

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