At BRITE, we perform basic and translational research focused on target validation and the discovery of novel small molecules with anticancer activity.
Breast cancer is the second leading cause of cancer deaths in US women, with African American women at a much higher risk of dying from this disease. Approximately 15%–20% of breast cancers have a triple-negative phenotype (TNBC), i.e., they lack expression of the estrogen receptor (ER) and the progesterone receptor (PR), and these cells do not overexpress Her2.
This type of breast cancer correlates with a very aggressive cancer, poor prognosis, and aggressive relapses. TNBC occurs at a higher incidence in young African American women. Currently available breast cancer therapies targeting ER or Her2 are ineffective against this subtype of breast cancer. Thus, new strategies are urgently needed for TNBC to reduce mortality and increase survival time.
Researchers at BRITE are working to identify and validate novel kinase targets critical for tumor growth and metastasis of TNBC. Inflammatory breast cancer disease models are also being studied at BRITE. The particular focus is on the efficacy of anticancer drugs and the characterization of the sensitivity of acquired therapeutic resistance to the drugs. The role of the Hh/GLI1 target pathway is also being studied.
BRITE researchers are investigating the use of G-protein coupled receptors as agents of human cancers. G-protein coupled receptors (GPCRs) are a diverse superfamily of heptahelical transmembrane proteins that traduce information from the surrounding environment to cells. They are activated by a wide range of bioactive molecules, including peptides, hormones, lipids, growth factors, ions, odorants, and photons. Activation of GPCRs alters the levels of intracellular second messenger systems by interacting with the trimeric guanine nucleotide-binding proteins (G-proteins).
Although many GPCR pathways linked to the dysregulation of pathophysiologic processes are well researched, little is known on the role they play in the development and progression of cancers in humans. Evidence accumulated in the last couple of years strongly suggests the existence of a link between the regulation of GPCR functions and human tumors. We are interested in characterizing the role of a family of proton-sensing GPCR dependent pathways that lead to a poorly understood cycle of abnormal growth in target cells to understand the role of GPCRs in human cancer.