New drug combination may help treat advanced prostate cancer
About 1 in 8 men are diagnosed with prostate cancer during their lifetime. Although many survive, it can develop into metastatic disease.
Approximately 1 in 8 men will be diagnosed with prostate cancer at some point in their lives, making it the second-leading cause of cancer-related death in men in the United States. Most prostate cancers are glandular in nature and require male hormones like testosterone for growth, which is why androgen receptor inhibitors are typically used as the primary treatment for metastatic prostate cancer.
However, these drugs often become ineffective as tumors adapt through a process called transdifferentiation, where they lose glandular genes and adopt different identities, becoming less susceptible to existing treatments.
A recent study published in JCI Insight by researchers at the University of Michigan has identified two pathways that can be simultaneously targeted to treat transdifferentiated prostate tumors. The team found that loss of genes TP53 and RB1 is associated with transdifferentiation, but the underlying reasons were not well understood.
Previous research demonstrated that BET bromodomain inhibitors can block pathways leading to alternate identity programs, but these drugs did not permanently stop disease progression. To address this, the researchers explored DNA methyltransferase (DNMT) inhibitors, which can reactivate genes, including glandular genes that change the identity of prostate cancers.
The study revealed that using both BET bromodomain and DNMT inhibitors together effectively suppressed the growth of prostate cancer cell lines and tumors in mice, more so than using either drug alone. This combination reversed a significant portion of gene expression changes in the tumors, indicating potential for improved treatment outcomes.
The researchers are now investigating which specific genes contribute to the antitumor effects observed and are looking for biomarkers to identify patients who would benefit from this drug combination. They also aim to explore whether this approach can prevent transdifferentiation before it occurs, potentially improving patient survival rates.
The researchers hope to conduct further clinical trials to test the efficacy of this drug combination in patients with transdifferentiated prostate cancer and to investigate its potential application to other types of transdifferentiated cancers.
Written by urgent.news from Medical Xpress's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
