Cytokine Disruption to Prevent Radiation Related Breast Damage
Abstract
Introduction: The complications of radiation dermatitis and fibrosis on breast cancer therapy are well established. To date the only proven approaches to reducing radiation toxicity are to decrease the treatment dose or field-size. Altering these has the potential of reducing treatment efficacy and is therefore not advised. We proposed that drugs aimed at the suppression of cytokines involved in the initiation and perpetuation of radiation-induced inflammation would be beneficial in preventing normal tissue toxicity after radiation therapy. Of particular interest were inhibitors of tumor necrosis factor-alpha plus or minus (TNFalpha plus or minus) interleukin 1 (IL-1) and transforming growth factor-beta (TGFbeta) Body: We examined a number of agents to suppress generally and specifically cytokines be believed affect the severity and progression of radiation fibrosis in women after breast irradiation. Importantly IL-1 related interventions consistently reduced cutaneous fibrosis after irradiation. We tested thin in mice deficient in the IL-1 receptor 1 in mice treated with IL-1 Ra the natural soluble IL-1 receptor blocker and in mice treated with non-specific drugs that reduce IL-1 expression including COX2 inhibitors. All interventions greatly reduced the rate of fibrosis development and the severity of the fibrosis. A manuscript describing the most important experiments has recently been accepted for publication in the Radiation Research Journal and is attached in appendix I. Key Research Accomplishments: We have identified 4 agents that should reduce radiation fibrosis in women treated for breast cancer. One curcumin is in development for national clinical testing. Others including IL-1 Ra are being evaluated as radiation protectors in case of bioterror.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA463851
Entities
People
- Paul Okunieff
Organizations
- University of Rochester