Secrets of aggressive, drug-resistant prostate cancer unravelled
doi:10.1038/nindia.2020.9 Published online 20 January 2020
Prostate cancer affects the prostate gland, which helps make semen. Male sex hormones, known as androgens, support the growth of prostate cancer cells by binding to androgen receptors. Anti-androgen drugs, designed to disrupt the function of androgens, have been linked to the birth of drug-resistant prostate cancer.
But has been unclear how the anti-androgen drugs cause prostate cancer. Now, researchers from the Indian Institute of Technology in Kanpur have discovered that long-term use of anti-androgen drugs increases the expression of a gene called SPINK1 in prostate cancer cells. The SPINK1 gene makes these cancer cells aggressive and drug-resistant1.
They found that this gene, known to encode a protein in the pancreas, also helps make cancer stem cells, which can self-renew, differentiate and grow like normal stem cells.
Using prostate-tumour-bearing mice and specific human prostate cancer cells, an international research team, led by Bushra Ateeq, showed that anti-androgen drugs such as Enzalutamide or Apalutamide increased the expression of the SPINK1 gene in prostate cancer cells.
They identified molecular pathways that eventually enhance the expression and activity of the SPINK1 gene in prostate cancer cells. They found a link between the increased levels of SPINK1 protein and the decreased levels of androgen receptors and REST, a complex known to suppress the activity of SPINK1.
Increasing the levels of REST using a specific compound lowered the levels of SPINK1, they report. This, in turn, robbed the cancer cells of their ability to trigger unbridled growth.
“Restoring REST levels may serve as an alternative strategy to treat patients with deadly, drug-resistant prostate cancer,” says Ateeq.
1. Tiwari, R. et al. Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer. Nat. Comm. (2020) doi: 10.1038/s41467-019-14184-0