Cellular Signature Unveiled as Key to Prostate Tumor Treatment Resistance

Researchers from the University of Michigan Rogel Cancer Center have discovered a distinct cellular signature that sheds light on why approximately one-third of prostate cancers are resistant to standard treatments. This breakthrough could pave the way for more personalized and effective therapeutic strategies.

The study focused on understanding why some patients with advanced prostate cancer do not benefit from androgen receptor pathway inhibitors (ARPIs) such as enzalutamide, which are commonly prescribed. While many patients respond positively to these drugs, a significant subset—termed 'extreme non-responders'—fail to see any improvement and tend to have a poorer prognosis.

By analyzing RNA sequencing data from multiple clinical trial datasets, the researchers identified a specific gene expression program associated with resistance to ARPI therapy. Notably, they found that patients with tumors exhibiting this signature derive substantial benefit from initiating chemotherapy with docetaxel earlier in their treatment course. Traditionally, docetaxel is used later, but these findings suggest rethinking treatment timing for certain patients.

Further investigation revealed that the kinase CDK2 plays a central role in regulating this resistance program. Targeting CDK2 with specific inhibitors in laboratory models was able to suppress the gene program and reduce tumor growth, indicating a promising new therapeutic direction.

Lead researcher Anbarasu Kumaraswamy explained that understanding the molecular underpinnings of treatment resistance allows for more tailored interventions. "Patients harboring this resistance signature could potentially receive more effective early intervention with chemotherapy, improving outcomes," he stated.

This research underscores the importance of molecular profiling in prostate cancer management, offering hope for overcoming resistance and personalizing treatment plans. The findings also open avenues for testing CDK2 inhibitors in clinical trials, which may benefit patients with resistant prostate tumors.

Published in npj Precision Oncology, this study highlights the significance of cellular signatures in predicting treatment responses and guiding therapeutic decisions.

Source: https://medicalxpress.com/news/2025-07-cellular-signature-prostate-tumors-resist.html