New Strategy May Help Treat Advanced Prostate Cancer
“Russia Today” – A new study has revealed a pharmaceutical strategy that may help combat prostate cancer that has become resistant to conventional treatments, after its cellular characteristics change and become more capable of withstanding therapy.
Prostate cancer in its advanced stages often relies on male hormones, primarily testosterone, for growth. Therefore, medications that block the signaling of these hormones are used, but the disease frequently develops resistance to treatment over time.
In some tumors, a change known as “cellular transformation” occurs, during which prostate cancer cells lose some of their original characteristics and acquire new traits that make them more resistant to treatment. Researchers from the University of Michigan found that simultaneously targeting two cellular pathways may be able to slow the growth of these tumors.
The researchers focused on prostate cancer associated with the loss of the TP53 and RB1 genes, two genes previously linked to cellular transformation, although the mechanisms underlying this process were not fully understood.
The team studied a group of prostate cancer cells to identify the changes that occur within them upon the loss of TP53 and RB1. The results showed that cellular transformation involves two main aspects: the loss of some of the cells’ glandular characteristics, and the activation of programs that drive them toward acquiring stem cell-like traits.
Dr. Joshi Alumkal, Professor of Internal Medicine, Hematology, and Oncology and a member of the Rogel Cancer Center, stated that researchers observed that the transformation is not limited to the loss of original cell characteristics, but is also accompanied by the activation of cellular programs that confer a different identity.
The team had previously tested drugs known as “BET bromodomain inhibitors,” which target pathways that help cancer cells acquire new characteristics. Experiments showed that these drugs can slow the growth of cancer cells, but do not eliminate them completely.
Therefore, the researchers turned to another class of drugs known as “DNA methyltransferase inhibitors” (DNMTs), which can reactivate some genes that prostate cancer cells lose during their transformation.
When the two classes were combined, researchers found that the drug combination was able to suppress the growth of prostate cancer cells more effectively than using either drug alone. The same result was replicated in experiments conducted on tumors implanted in mice.
Dr. Will Stork, a researcher in Alumkal’s laboratory, said that using the two drugs together reversed a significant portion of the changes in gene activity within the tumors, and led to a marked decrease in their growth, even at low doses.
The results are still in the pre-clinical stage, as the study was conducted on cancer cells and animal models, so the effectiveness of this combination in patients cannot yet be confirmed.
Researchers are currently working to identify the genes behind the anti-tumor effect, as well as searching for biomarkers that could be used to determine which patients might benefit from this treatment.
The team is also trying to determine whether the risk of cellular transformation can be detected early and prevented before it occurs, which could pave the way for more effective therapeutic interventions.
