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Discovery of a new candidate drug to overcome cabazitaxel-resistant gene signature in castration-resistant prostate cancer by in silico screening

Prostate Cancer & Prostatic Diseases Oct 05, 2021

Hongo H, Kosaka T, Suzuki Y, et al. - Pimozide, which targets AURKB and KIF20A, looks to be a viable medication for overcoming cabazitaxel (CBZ) resistance in castration-resistant prostate cancer (CRPC).

  • Pimozide was found as a promising prospective medication for CBZ-resistant CRPC.

  • On DU145CR cells, pimozide demonstrated a substantial antitumor impact.

  • Furthermore, the combination of pimozide and CBZ showed a synergistic effect on DU145CR cells in vitro and in vivo.

  • AURKB and KIF20A were identified as potential pimozide targets in CBZ-resistant CRPC using microarray analysis.

  • When compared with a non-CBZ-resistant cell line, DU145CR had considerably higher AURKB and KIF20A expression.

  • In DU145CR xenograft tumors, inhibiting AURKB and KIF20A had an antitumor impact.

  • Higher AURKB and KIF20A expression was associated with a worse prognosis in the TGCA prostate cancer cohort.

  • AURKB and KIF20A expression were greater in CBZ-resistant prostate cancer tissues at the institution.

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