Research indicates that it could be possible to restore drug-resistant neuroendocrine prostate cancer to a state that responds to treatment. This may be achieved by depletion of a certain protein in cancer cells.
This is based on a recent study by the University of Eastern Finland. The study found that this protein, DPYSL5, is expressed in neuroendocrine prostate cancer.
Prostate cancer is the most common cancer in men, and the second most common cause of cancer death in Western countries. The growth of prostate cancer often depends on androgens, and the effect of androgens is sought to be reduced by drug therapy, especially in metastatic prostate cancer.
There is a concern that cancer cells can become resistant to drugs, resulting in castration-resistant prostate cancer.
Second-generation antiandrogens, drugs that inhibit the activity of the androgen receptor, have been developed as a treatment alternative for castration-resistant prostate cancer. A continuing concern is where one in four castration-resistant prostate cancers develop into treatment-induced neuroendocrine cancer, which is aggressive and typically leads to death within a year of the diagnosis.
Neuroendocrine prostate cancer cells usually do not have androgen receptors, and currently no treatment is available for this group of patients. This could change with the identification of a protein affecting neuroplasticity that promotes the development of neuroendocrine prostate cancer.
The University of Eastern Finland has explored the differentiation, plasticity and development of drug resistance in cancer cells. In relation to this, researchers have discovered a potential new target for drug development in neuroendocrine prostate cancer.
The protein, DPYSL5, is expressed especially in this cancer type and could therefore be a suitable target for drug therapy. Normally, the DPYSL5 protein regulates the development of neurons in the brain and is not expressed in other parts of the body.
The research has found that antiandrogen treatment caused the DPYSL5 protein to be expressed in prostate cancer cells. As a result, these cells acquired stem cell-like and neuron-like properties observed in neuroendocrine prostate cancer cells. Studies showed how DPYSL5 promoted cell transformation by activating the PRC2 complex, which caused cancer cells to go into a stem cell-like state.
DPYSL5 also caused cancer cells to form extensions similar to those found in neurons, which helped them to invade the surrounding tissue.
With the depletion of DPYSL5 inactivated the PRC2 complex, this prevented the formation of neuron-like extensions, and restored cells to a state where antiandrogen treatment was once again effective in preventing cell division. The findings can be used for the development of new cancer drugs.
The research appears in the journal Nature Communications Biology, titled “DPYSL5 is highly expressed in treatment-induced neuroendocrine prostate cancer and promotes lineage plasticity via EZH2/PRC2.”
