BUB1B and CENP-E: A New Vulnerability in Enzalutamide-Resistant Prostate Cancer

A new preclinical study published in Cancer Research has identified a possible way to attack prostate cancer that has become resistant to castration and enzalutamide. The work focuses on BUB1B, a protein involved in controlling cell division, and CENP-E, one of the proteins it helps regulate.

When researchers lowered BUB1B levels, resistant prostate cancer cells had trouble dividing. When they increased BUB1B, the opposite happened: cancer cells were better able to keep growing despite hormone deprivation and became more resistant to enzalutamide.

The researchers found that BUB1B needs to be active to drive resistant tumour growth. Its main partner appears to be CENP-E, a protein that helps cells divide correctly. When this BUB1B–CENP-E pathway was disrupted, resistant cancer cells were much less able to keep growing.

This opened a practical therapeutic route. Instead of trying to block BUB1B directly, the researchers used GSK-923295, a drug that inhibits CENP-E and has already been tested in humans. In the laboratory, the drug made resistant prostate cancer cells more sensitive to enzalutamide and slowed the growth of enzalutamide-resistant tumours in mice.

What makes the study interesting is that it points to a different way of attacking resistance. Instead of trying to block the androgen receptor again, it targets the machinery cancer cells need to keep dividing.

The results are still preclinical, so there is no evidence yet that CENP-E inhibition will work in men with metastatic castration-resistant prostate cancer. Still, the fact that a CENP-E inhibitor has already entered clinical testing could make this pathway easier to explore than a completely new target.

Source.