Explaining EZH2 mechanism and epigenetic regulation to non-specialists and patients

Dr. Agarwal asks Dr. Morgans how she explains the EZH2 mechanism and epigenetic regulation to non-specialists and patients with varying degrees of health literacy. Dr. Morgans takes a deliberately simple approach, distinguishing genetic from epigenetic concepts: genetic refers to the DNA sequence itself—the order of the letters that express themselves—while epigenetic changes affect how those genes are read and expressed without altering the underlying sequence. EZH2 inhibition acts at this epigenetic level to slow the harmful changes occurring in cancer cells.

She also contrasts EZH2 inhibitors with chemotherapy, which patients commonly recognize. Chemotherapy kills rapidly dividing cells through a direct cytotoxic effect. By contrast, EZH2 inhibitors reprogram gene expression to restore normal cell-cycle control, block proliferation, and prevent transformation of cancer cells into more aggressive phenotypes.

Finally, Dr. Morgans differentiates EZH2 inhibitors from androgen receptor (AR)–targeted therapy. AR inhibitors block testosterone stimulation of prostate cancer cells, whereas EZH2 inhibitors work upstream by changing which genes are turned on or off, potentially resensitizing tumors to AR inhibition or maintaining their sensitivity. The two work together but represent distinct mechanisms of action.

In the next episode, "Awareness, access, and integrating clinical trial discussions into routine care," Dr. Agarwal shares strategies for raising awareness of EZH2 and the MEVPRO trials and integrating trial conversations into routine practice.