It might be possible to revive drug-resistant neuroendocrine prostate cancer to a state that responds to treatment by depletion of a certain protein in cancer cells. A recent study by the University of Eastern Finland found that this protein, DPYSL5, is expressed in neuroendocrine prostate cancer.

Prostate cancer is probably the most common cancer in men, and the second most typical explanation for cancer death in Western countries. The expansion of prostate cancer often is dependent upon androgens, and the effect of androgens is sought to be reduced by drug therapy, especially in metastatic prostate cancer. Nevertheless, cancer cells can develop into proof against drugs, leading to castration-resistant prostate cancer.

Second-generation antiandrogens, that are drugs that inhibit the activity of the androgen receptor, have been developed as a treatment alternative for castration-resistant prostate cancer. Unfortunately, recent studies have shown that about one in 4 castration-resistant prostate cancers become what’s referred to as treatment-induced neuroendocrine cancer, which is aggressive and typically results in death inside a yr of the diagnosis. Neuroendocrine prostate cancer cells normally don’t have androgen receptors, and currently no treatment is accessible for this group of patients.

A protein affecting neuroplasticity promotes the event of neuroendocrine prostate cancer

On the University of Eastern Finland, the Ketola Lab led by Academy Research Fellow Kirsi Ketola explores the differentiation, plasticity and development of drug resistance in cancer cells.

In the brand new study researchers on the Ketola Lab discovered a possible latest goal for drug development in neuroendocrine prostate cancer. The protein, DPYSL5, is expressed especially on this cancer type and will subsequently be an appropriate goal for drug therapy.

The Ketola Lab collaborated with the University of British Columbia in Canada, utilising the university’s extensive collection of neuroendocrine prostate cancer patient tumor samples to confirm the expression of the DPYSL5 protein in these samples.

Normally, the DPYSL5 protein regulates the event of neurons within the brain and isn’t expressed in other parts of the body. Nevertheless, the researchers now found that antiandrogen treatment caused the DPYSL5 protein to be expressed in prostate cancer cells. Consequently, these cells acquired stem cell-like and neuron-like properties observed in neuroendocrine prostate cancer cells.

DPYSL5 promoted cell transformation by activating the PRC2 complex, which caused cancer cells to enter a stem cell-like state. DPYSL5 also caused cancer cells to form extensions much like those present in neurons, which helped them to invade the encompassing tissue. Nevertheless, depletion of DPYSL5 inactivated the PRC2 complex, prevented the formation of neuron-like extensions, and restored cells to a state where antiandrogen treatment was once more effective stopping cell division.

The findings may be used for the event of recent cancer drugs.

Next, we shall be using novel imaging methods available at our Cell and Tissue Imaging Unit to screen drugs that inhibit the function of DPYSL5.”

Kirsi Ketola, Academy Research Fellow

Published in Nature Communications Biology, the study was funded by the Research Council of Finland, the Sigrid Jusélius Foundation, the Finnish Cultural Foundation, the Finnish Cultural Foundation North Savo Regional Fund, and the Cancer Foundation of Finland.