Prostate cancer is the most common male cancer, affecting 1 out of 6 American men. Current detection and diagnosis methods include blood prostate-specific antigen levels, digital rectal exam, and biopsies. Based on the results, treatment course may include “watchful waiting” or active surveillance, followed by surgery, radiation, chemo- or hormone therapy as necessary. Therapeutic approaches to date are not specific, and may not target the correct ‘type’ of prostate cancer based on the patient’s genetic predisposition, and are associated with harsh side effects, which discourage patients from being seeking treatment.
Researchers at the University of Michigan have identified a specific microRNA and small molecules that target Enhancer of Zeste Homolog 2 (EZH-2) and inhibit its expression. EZH-2 is a histone methyltransferase which belongs to the polycomb group protein family, and is overexpressed in aggressive solid tumors. EZH-2 contributes to the epigenetic silencing of target genes and regulates the survival and metastasis of cancer cells. In human prostate tumors, the expression of a specific microRNA, miR-101, decreases during cancer progression, paralleling an increase in EZH-2 expression. The genomic loss of miR-101 in cancer may lead to overexpression of EZH-2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression.
Applications and Advantages
- Treatment of prostate cancer patients, especially during the “watchful waiting” period
- Ongoing drug discovery program includes target identification and validation and assay development