PPAR Alpha and Fenofibrate for the Prevention or Treatment of Breast Cancer Brain Metastasis
Abstract
As treatments for the primary breast tumors and metastasis to other organs get better and prolong the life of breast cancer patients, doctors are seeing more patients whose breast cancer has spread to the brain; up to 46% of metastatic patients with triple-negative breast cancer and up to 37% of metastatic patients with HER2+ breast tumors are expected to eventually develop metastases in the brain. Because most therapeutic drugs that effectively treat breast cancer in other parts of the body cannot get into the brain, the incidence of brain metastasis is expected to continue to increase. Brain metastasis has therefore been referred to by some as the “final frontier” for breast cancer treatment. Unfortunately, brain metastasis causes significant morbidity and mortality for the patient, with only 20% of patients with brain metastases remaining alive 1 year following diagnosis. At present, treatment options for brain metastasis are limited, but usually include the use of brain radiation to control progression of the disease. While the use of brain radiation is effective for up to 65% of patients, a significant proportion of patients who receive this life-prolonging therapy will often develop a progressive cognitive impairment as a result of their treatment. There is a dire need to find better ways to safely and effectively treat brain metastasis. Prior studies have shown that administration of the drug fenofibrate can prevent the cognitive decline that results from whole brain irradiation in animal models. In the current study, we propose to determine whether a commonly used drug, fenofibrate, can be used to help treat brain metastasis. In addition to its known prescribed role, fenofibrate possesses additional activities that cause decreased growth of several types of tumor cells; we now want to see if it can also inhibit breast cancer metastatic cells and their tumors in the brain. In addition, because fenofibrate can prevent activation of normal cells in the brain that can facilitate the development of brain metastases by breast cancer cells, we will also assess whether fenofibrate can prevent the initial establishment of the brain metastases. Because fenofibrate is already prescribed by doctors for other conditions and shown to be safe for patients, we believe that success of our studies could allow our clinical collaborator to rapidly develop clinical trials to determine whether fenofibrate can prolong the life and/or improve the quality of life of brain metastasis patients, including those receiving any kind of brain irradiation. Our studies are therefore responsive to the overarching challenges of “Eliminate the mortality associated with metastatic breast cancer” and “Revolutionize treatment regimens by replacing them with ones that are more effective, less toxic, and impact survival.” In the latter case, we will revolutionize treatment regimens, not by “replacing” a current treatment, but by adding a drug that may render a standard treatment more safe and effective for patients. While our focus in these studies is on the use of fractionated whole brain irradiation, we note that any additive or synergistic effect of fenofibrate on tumor growth would be beneficial regardless of radiation modality used to treat the brain tumor. Furthermore, if fenofibrate can successfully prevent the establishment of brain metastases, it may have use as an adjunct therapy for patients at highest risk for the development of brain metastases (i.e., patients with triple-negative or HER2+ tumors).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010326
Entities
People
- Linda Metheny-barlow
Organizations
- United States Army
- Wake Forest University