Combined MEK5 inhibition and radiation therapy for prostate cancer treatment This technology reveals that inhibition of mitogen-activated protein/extracellular-signal activated kinase kinase 5 (MEK5) preferentially sensitizes prostate malignant cells to radiotherapy.
Radiotherapy is commonly used to treat prostate cancer. However, malignant cells become radioresistant through tumor-intrinsic pro-survival pathways and upregulation of DNA repair pathways. Higher doses of ionizing radiation improve local control, but must be limited for toxicity to noncancerous tissues. Therefore, there is a clinical need to lower the radiation dose while still preserving therapeutic index.
This technology uses short hairpin RNA interference (shRNA) to inhibit MEK5 in prostate cancer cells, resulting in substantial radiosensitization. MEK5 inhibition reduces activation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and protein kinase B (AKT), leading to diminished DNA repair and radio-resistance. As MEK5 protein is not detected in normal prostate epithelial cells, inhibition is not expected to radiosensitize normal tissue, thus providing significant therapeutic benefit to prostate cancer patients.
This technology has been validated with human cancer cell lines and animal models.
Constantinos G. Broustas, Ph.D.
IR CU20266
Licensing Contact: Ron Katz