Surprising Cause Of Treatment Resistance In Prostate Cancer Cells

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A hormone supplement routinely used with prostate cancer patients after radiotherapy may increase the likelihood of the cancer’s return, according to a University of York study.

In earlier research, investigators discovered stem cells within the cancer are radiotherapy resistant. However, why stem cells survived the therapy when other parts of the cell died was unclear. Now, after studying cancerous cells from prostate cancer patients, researchers realize stem cell proteins called SMARCs help the cancer’s “core” stay alive.

What surprised scientists was the realization that cancer cells treated in the lab with glucocorticoid hormone were especially resistant to cancer treatment. This was troubling since glucocorticoid hormone tablets are typically prescribed for radiotherapy patients to boost their energy levels.

“This was a really unexpected result of our investigation, so we took a slightly different direction in order to find out why these stem cells would become more resistant to cancer treatment,” said Professor Norman Maitland, University of York.

Maitland and colleagues came to realize that tiny molecules called MicroRNAs are involved. MicroRNAs are found in all normal cells, exist at low levels in cancer stem cells, and their levels can be influenced by hormones, such as glucocorticoid. The researchers also saw that fluctuations in the MicroRNA population affected the amount of SMARCs in stem cells—fewer MicroRNA leads to a SMARC increase.

“When more glucocorticoid hormones are ingested, the levels of MicroRNAs decrease even further, resulting in an increase in SMARCs. These SMARC proteins wind up chromosomes inside the cancer cells to make them resistant to treatment,” says Maitland.

After the research team blocked natural levels of glucocorticoids in patients, they noted an increase in MicroRNAs, and measured an expected decrease in SMARC proteins. This means it’s possible that standard radiotherapy doses could kill more cancer stem cells, eliminating the root of cancer recurrence following treatment. Future studies will include clinical trials to determine whether blocking glucocorticoid in patients, instead of boosting it, improves radiotherapy success rates.

Source: Science Daily

 

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