Scientists identify drug combination that could slow the growth of treatment-resistant prostate cancer

Researchers at the University of Michigan have identified a combination of two drugs that is significantly more effective at slowing the growth of prostate tumors resistant to standard treatment. The findings were published in the scientific journal JCI Insight.

Prostate cancer often depends on male sex hormones, including testosterone, known as androgens. As a result, drugs that block androgen activity are among the main treatments for advanced disease. However, their initial effectiveness almost always eventually fades: the tumor develops resistance to therapy and continues to grow.

In some cases, cancer cells essentially change their “identity.” They lose the characteristics of glandular tissue typical of conventional prostate cancer and acquire properties associated with other cell types. This process, known as transdifferentiation, allows tumors to rely on alternative biological programs to survive.

The researchers found that at least two interconnected processes drive this transition: cancer cells lose the activity of genes characteristic of glandular tissue while simultaneously activating stem cell-related programs. Previous research has also linked transdifferentiation to the loss of the tumor suppressor genes TP53 and RB1.

To target these altered cells, the researchers combined two types of drugs. The first was a class of BET bromodomain inhibitors, which can block the activation of alternative cell-development programs.

The second was DNA methyltransferase (DNMT) inhibitors, which can reactivate genes that have been silenced or lost by tumor cells.

On their own, BET inhibitors only slowed the growth of cancer cells without destroying them. However, the combination of the two drugs suppressed tumor growth much more effectively. The researchers observed a similar effect in mice implanted with prostate tumors.

The combined treatment also partially reversed changes in gene activity that had occurred in the tumor cells. The combination was well tolerated by the mice and produced a substantial reduction in tumor growth even at doses significantly lower than those recommended for the individual drugs.

Both classes of drugs are already being investigated or used in medicine. Some DNMT inhibitors, for example, have been approved by the U.S. Food and Drug Administration (FDA) to treat certain types of blood cancer. However, the effectiveness of this particular combination against prostate cancer still needs to be tested in humans.

Follow NEWS.am Medicine on Facebook and Twitter