Combination Therapy Holds Promise for Advanced Prostate Cancer Treatment

Decitabine, a prostate cancer drug, that inhibits DNA methylation, effectively cuts tumor growth in prostate cancer with neuroendocrine features or loss of the gene RB1. DS-7300a- another drug used in prostate cancer treatment, is an antibody-drug conjugate that targets B7-H3 receptors, elevated in prostate tumors. Researchers found that the combination of decitabine and DS-7300a was more effective in slowing the growth of tumors in patients with advanced prostate cancer.

This study was led by researchers from Dana-Farber Cancer Institute using patient-derived preclinical models of advanced prostate cancer (1^✔ ✔Trusted Source
Targeting DNA methylation and B7-H3 in RB1-deficient and neuroendocrine prostate cancer

Go to source).

Treatment Strategy in Advanced Prostate Cancer

Epigenetic changes can cause prostate cancer to resist treatment by switching genes on or off. One epigenetic mechanism tags genes with DNA methylation marks. This process is mediated by molecules called DNA methyltransferases. These tags can alter gene expression in ways that promote tumors to grow and transition into advanced forms of the disease.

The inhibition of DNA methylation with decitabine, a medicine used in the treatment of certain blood cancers, slows tumor growth specifically in a subset of advanced prostate cancers that have neuroendocrine features or loss of the gene RB1.

It also results in decreased methylation and elevated expression of a gene that produces a receptor called B7-H3. This receptor is the target of an antibody-drug conjugate currently in evaluation in clinical trials called DS-7300a.

In prostate cancers with high levels of B7-H3, DS-7300a was effective on its own. However, DS-7300a alone was less effective when B7-H3 levels were low. The researchers observed that when the drugs are combined, decitabine sensitizes tumors to DS-7300a and improves efficacy.

Patients with advanced prostate cancer with tumors harboring RB1 gene loss or neuroendocrine features often have a poor prognosis and limited treatment options. This research opens the door to a potential treatment strategy geared specifically toward this population that involves decitabine, B7-H3 targeted therapy, or the two in combination.

Advertisement

Reference:

1. Targeting DNA methylation and B7-H3 in RB1-deficient and neuroendocrine prostate cancer - (https://www.science.org/doi/10.1126/scitranslmed.adf6732)

Source-Eurekalert