TITLE:
Development of a Protein Therapeutic That Targets the TMPRSS2:ERG4 Break Region in Prostate Cancer Cells: A Modular Design Approach
AUTHORS:
Alan Chant, Joshua L. Weiss, Jack A. Kucine, Christina M. Kraemer-Chant
KEYWORDS:
Zinc Finger (ZF) Proteins, TMPRSS2:ERG4 Gene Fusion, ZiFit Binding Prediction Tool, Uracil DNA Glycosylase (UDG2), DNA Binding Specificity, Chromosomal Translocation/Breakpoint Region, Protein-DNA Interactions, Cancer Gene Fusions/Oncogenes
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.16 No.7,
July
29,
2025
ABSTRACT: Prostate cancer is reported to be the second most common cancer in men. At this time, there exist over 20 FDA-approved drugs for the treatment of prostate cancer. These include alkylating agents, anchracenedione, anti-androgens, antimicrotubule agents, autologous cellular immunotherapy, conjugated estrogens, GnRH (Gonadotropin-Releasing Hormone) analogues and GnRH antagonists (Source: FDA.gov http://www.empr.com/fda-approved-prostate-cancer-drug-treatments/article/123619/#). With recent developments in the detection of prostate cancer, and with the growing population of men who are reaching the age where prostate cancer becomes a significant health issue, the necessity for a drug that targets prostate cancer cells with high specificity and selectivity has increased. The basic premise of our therapeutic, which is designed to bind tightly to a DNA sequence found only in prostate cancer cells, consists of a molecular motor, a small number of zinc finger proteins, and a C-terminal lysine tail. The irreversible binding of our therapeutic with the target DNA is predicted to regulate transcription of the gene and ultimately target the cell for death, thus reversing the proliferation of prostate cancer cells containing that sequence of DNA.