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Mechanism of PIM1 Kinase-Mediated Radiosensitization for Prostate Cancer Treatment
Radiotherapy is a standard treatment for localized prostate cancer, but there remains significant room for improvement since treatment failure and mortality remain high. PIM1 kinase is an oncogenic protein that is elevated in prostate cancer and causes cell survival through anti-apoptotic effects and increased cell proliferation through cell cycle manipulation. Inhibiting PIM kinase kills prostate cancer cells and decreases their proliferation.
In his 2016 RSNA Research Scholar Grant, Austin Kirschner, MD, PhD, and his team studied several human prostate cancer cell lines by in vitro cultures and in vivo mouse models that were treated with oral PIM kinase inhibitors. They investigated PIM inhibition alone and in combination with chemotherapy, hormone therapy and radiotherapy to treat prostate cancer. They found that PIM inhibition causes an anti-tumor treatment effect, but the combination treatments are much more effective. They also discovered that PIM inhibition causes radiosensitization of the prostate cancer, making the prostate cancer cells more sensitive to the killing effects of radiotherapy.
“Our preclinical models show that inhibiting PIM kinase in human prostate cancer causes it to become more sensitive to radiotherapy and die,” Dr. Kirschner said. “There are oral PIM kinase inhibitors in clinical trials for hematologic human malignancies. We hope to perform a clinical trial to study the combination of prostate radiotherapy with these PIMinhibiting drugs with the goal of increasing the effectiveness of radiotherapy for aggressive localized prostate cancer.”