Researchers at the Fred Hatch Cancer Center have discovered a molecular regulator that may help determine whether prostate cancer will respond to treatment or turn into a more aggressive and drug-resistant form.
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The study, published in the journal Nature, revealed that a single molecule of transfer RNA (tRNA) can play an important role in identifying prostate cancer cells and influencing their response to treatment.
Prostate cancer is one of the most common cancers among men. In its early stages, it relies on the androgen receptor, a protein that promotes tumor growth and is targeted by many treatments. However, some tumors lose their dependence on this receptor over time, becoming more aggressive and less responsive to treatment.
Yoon Soo Kim, the study's lead author and a postdoctoral researcher at the Fred Hutch Center, sought to understand the mechanisms behind this transformation. The study focused on the role of tRNA molecules, which are involved in protein synthesis within cells.
The researchers used prostate cancer cells, animal models, and tumor samples taken from patients, and found that levels of a specific tRNA molecule known as tRNA1Arg(UCU) were high in cells dependent on the androgen receptor, while they decreased in cells that had lost their dependence on the receptor and become resistant to treatment.
Experiments have shown that supplying treatment-resistant tumors with this molecule can restore their sensitivity to therapies that target the androgen receptor, suggesting that a single tRNA molecule may be able to influence cell identity and determine whether a cell will remain sensitive to treatment or become more aggressive.
Andrew Hsieh, co-author of the study and professor at the Fred Hatch Centre, said the findings reveal a new role for tRNA molecules in cancer biology, after it was thought that they primarily performed functions related to protein synthesis and cell maintenance.
The potential implications of these findings are not limited to prostate cancer, as researchers believe the same mechanism may exist in other types of cancer where cell identity changes after treatment, such as lung cancer and breast cancer.
Researchers are currently exploring the possibility of using tRNA molecules as biomarkers to help identify tumors most likely to resist treatment, or as targets for developing new therapies for aggressive prostate cancer.
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