Anew study has revealed a drug strategy that may help combat prostate cancer that loses its response to traditional treatments, after the characteristics of its cells change and become more resistant to treatment.
Advanced prostate cancer often relies on male hormones, primarily testosterone, for growth. Therefore, drugs that block the signaling of these hormones are used, but in many cases, the disease 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 ones that make them more resistant to treatment. Researchers at the University of Michigan found that targeting two cellular pathways simultaneously may be able to slow the growth of these tumors.
The researchers focused on prostate cancer, which is associated with the loss of the TP53 and RB1 genes, two genes previously linked to cellular transformation, but the mechanisms behind this process were not fully understood.
The team studied a group of prostate cancer cells to find out what changes occur within them when the TP53 and RB1 genes are lost. The results showed that the cellular transformation involves two main aspects: the loss of some of the cells' glandular characteristics, and the activation of programs that drive them to acquire stem cell-like properties.
Dr. Joshi Alomkal, professor of internal medicine, hematology and oncology and a member of the Rogel Cancer Center, said that researchers have 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 give them a different identity.
The team had previously tested drugs known as "BET (bromine domain) inhibitors," which target pathways that help cancer cells acquire new characteristics. The experiments showed that these drugs can slow the growth of cancer cells, but do not eliminate them completely.
Therefore, researchers turned to another class of drugs known as DNA methyltransferase inhibitors (DNMTs), which can reactivate some of the genes that prostate cancer cells lose during their transformation.
When the two drugs were combined, the researchers found that the drug combination was more effective at suppressing the growth of prostate cancer cells than either drug alone. The same result was replicated in experiments conducted on tumors implanted in mice.
Dr. Will Stork, a researcher at the Alumcal Laboratory, said that using the two drugs together reversed a large portion of the changes that occur in gene activity within tumors, and also led to a significant decrease in their growth even when low doses were used.
The results are still in the pre-clinical trial 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 can be used to identify patients who may benefit from this treatment.
The team is also trying to find out if it is possible to detect the risk of cellular transformation early and prevent it before it occurs, which could open the door to more effective therapeutic intervention.
The researchers hope to move these results into clinical trials to test the drug combination in prostate cancer patients, as well as study the possibility of using the same strategy in other types of cancer that can undergo a similar cellular transformation, such as some lung and pancreatic cancers.
