April 11, 2019

Pathways of radiosensitization

Austin Kirschner and colleagues demonstrate how a hormone therapy for prostate cancer improves radiation’s tumor-killing power.

by Leigh MacMillan

Androgen deprivation (hormone) therapy for prostate cancer sensitizes cancer cells to radiation and improves radiation’s tumor-killing power. Second-generation anti-androgen agents, such as enzalutamide, are used to treat both hormone-sensitive and -resistant metastatic prostate cancer and are being investigated as first-line therapeutics in combination with radiation therapy.

Austin Kirschner, MD, PhD, and colleagues have studied the mechanism of radiation sensitization for enzalutamide using multiple models of human prostate cancer.

They report in PLOS ONE that enzalutamide radiosensitizes both androgen-sensitive and -resistant cultured prostate cancer cells in vitro and in mouse models. Enzalutamide also radiosensitized a patient-derived prostate tumor that had failed multiple treatments in a mouse model. The researchers found that enzalutamide inhibits DNA damage repair of double-stranded breaks and halts the cell cycle.

The study provides mechanistic data and supports the use of enzalutamide concurrently with radiation therapy to enhance prostate cancer treatment.

This research was supported by Astellas Pharma Global Development and by the Vanderbilt Clinical Oncology Research Career Development Program (National Institutes of Health grant CA090625).