Brain metastasis occurs in 15-30% of patients with inflammatory breast cancer (IBC), a very aggressive and highly metastatic variant of breast cancer. Brain metastasis disproportionately affects those patients with HER2+ and basal-like/triple-negative breast cancer (TNBC) subtypes. Despite significant advances in the systemic treatments of breast cancer, only minimally active drugs are currently available for patients with breast cancer brain metastasis. The prognosis for patients with breast cancer brain metastasis is dismal with a survival time ranging from 5 weeks for untreated patients to 6 months for patients given multimodality treatment. Therefore, novel and effective therapeutic approaches are urgently needed for such patients. Understanding the biology and mechanisms underlying metastatic dissemination to the brain are crucial for developing new therapies to treat breast cancer brain metastases. We have developed unique preclinical mouse models of brain metastasis from TNBC and HER2+ IBC cells and used these models to identify key regulators of metastatic dissemination to brain. In this seminar, I will present a brief background on brain metastasis and IBC, discuss the novel models of brain metastasis that we developed in our lab, and provide insights into the molecular mechanisms of some of the top candidate proteins, that we identified through proteomic and transcriptomic approaches, that are associated with aggressiveness and metastasis in IBC.
Dr. Bisrat Debeb is an Assistant Professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Debeb received his Doctor of Veterinary Medicine (DVM) degree from Addis Ababa University, his Masters from Tuskegee University, and his Ph.D. from Texas A&M University. He completed his postdoctoral training at MD Anderson Cancer Center. The major research interests of Dr. Debeb’s lab are understanding molecular and cellular mechanisms underlying the unique pathobiology of inflammatory breast cancer (IBC), a rare but highly metastatic lethal form of primary breast cancer, and identification of molecular determinants of breast cancer brain metastasis. His lab conducts both basic and translational breast cancer research with an overarching goal of developing novel and effective therapeutic strategies to improve survival of patients with aggressive breast cancer and brain metastasis. Current efforts in his lab include developing mouse models of brain metastasis, identification of novel drivers of IBC tumorigenesis and brain metastasis, and evaluation of serum from IBC patients to identify biomarkers of aggressiveness, brain metastasis and therapy resistance.