Enhancing Outcomes of Radiation Therapy for Prostate Cancer
Abstract
Prostate cancer remains the most common malignancy and the third leading cause of cancer-related death for men in the United States. Every year, tens of thousands of men in the United States undergo treatment with radiation therapy as a primary treatment for localized prostate cancer. While results are often excellent, approximately one third will develop recurrence and up to a third of men with recurrence will die of their disease, particularly men diagnosed initially with more aggressive disease. In addition, thousands of men receive radiation therapy following radical prostatectomy to try and prevent recurrence or for palliation of metastatic disease. Our goal is to develop therapies that, when used concurrently with radiation, provide clinical benefit to patients and enhance the number of cures with low toxicity. Based on the literature and our preliminary data, we hypothesize that two major pathways that may contribute to resistance to radiation therapy are RET and FGFR signaling. These signaling receptors are both present on prostate cancer cells, and the activators of signaling are present in prostate cancer tissues. Both of these receptors are inhibited by lenvatinib, a multikinase inhibitor already in the clinic for treatment of thyroid and renal cancer. If both pathways are important in resistance to radiation, the ultimate goal will be to determine whether lenvatinib treatment at the time of radiation will enhance the rate of long-term cures of prostate cancer by radiation therapy. If, on the other hand, inhibition of FGFR signaling is more important than RET signaling in radiation resistance, then there are several FGFR inhibitors that are currently in clinical trials that could be evaluated for clinical utility. If successful, our studies will provide the preclinical rationale to support a clinical trial of this approach to enhance radiation therapy outcomes in men with prostate cancer, particularly those with high aggressive disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810299
Entities
People
- Sean McGuire
Organizations
- Baylor College of Medicine
- United States Army