Minor intron splicing is critical for survival of lethal prostate cancer-Augspach et al.
Description
Men with androgen receptor-negative castration-resistant prostate cancer (ARN CRPC) do not benefit from androgen receptor-directed therapies, face low survival rates, and have few alternative therapeutic options. Addressing this unmet clinical need requires new approaches to identify this more aggressive form of disease early on and to treat it effectively. A recent study showed that the minor spliceosome (MiS) is crucial for PCa progression as it regulates expression of minor intron-containing genes (MIGs) that execute molecular programs downstream of oncogenes. Moreover, the study showed that RNAi based MiS inhibition reduced tumor burden in different PCa models, including ARN-CRPC. Crucially, while it did not affect non-cancer cells, this approach was more successful at blocking proliferation and survival of ARN-CRPC cells compared to the current state-of-the-art therapies. Taken together, MiS has emerged as a vulnerability of ARN CRPC that holds considerable therapeutic promise. To advance this seminal finding from the bench to the bedside, this study will explore various strategies to improve siU6atac in vivo delivery to PCa. The results of the proposed experiments will be a step closer to translate U6atac knockdown and MiS inhibition to an effective tool in cancer treatment