The article reports on a study published in JCI Insight by researchers at the University of Michigan, which identifies a potential new treatment strategy for metastatic prostate cancer that has undergone transdifferentiation—a process where cancer cells lose glandular characteristics and adopt alternative cellular identities, enabling them to evade androgen receptor inhibitors. The researchers found that the loss of the genes TP53 and RB1 is linked to this transdifferentiation. They discovered that combining BET bromodomain inhibitors, which interfere with pathways allowing prostate cancer cells to activate alternative identity programs, with DNMT inhibitors, which can reactivate silenced glandular genes, more effectively suppressed the growth of prostate cancer cell lines and tumors in mice than either drug class alone. Read the full article here.

The study suggests that targeting both the activation of alternative identity programs and the restoration of lost glandular gene activity may be more effective in treating transdifferentiated prostate cancer than targeting a single pathway. The researchers observed a significant reduction in tumor growth in mouse models at lower drug doses, indicating good tolerance. Moving forward, the team aims to identify the specific genes responsible for the antitumor effects, develop biomarkers to pinpoint patients most likely to benefit from the combination therapy, and explore the possibility of preventing transdifferentiation before it occurs. Additionally, they are interested in testing this dual-drug approach against other cancers that undergo similar transdifferentiation processes, such as lung and pancreatic cancers. Source: Michigan Medicine - University of Michigan.

This is a summary. Read the original at sciencedaily.com.