Targeted Epigenetic Therapy for Triple-Negative Breast Cancer

DESCRIPTIONprovided by applicantTriple negative breast cancerTNBCis one of the most aggressive forms of human cancerand currently has no targeted therapyChemotherapy is the only available treatment for TNBC patientsbut is deleterious and not effective once tumor spreadsTNBC represents a major unmet medical needaboutof breast cancer incidenceswomen worldwide inare TNBCTNBC disproportionally affects women of African and Hispanic descentand younger women as early as in theirsandof breast cancer in people with an inherited BRCAmutation is found to be TNBCBreast cancer is a highly heterogeneous disease with five major subtypesluminal Aluminal BErbBnormal likeand basal likeBasal like breast cancer is defined by markers characteristic of basal myoepithelial cellsand by lack of expression of three receptorsi eestrogen receptorERprogesterone receptorPRand human epidermal growth factor receptorHerneuhence commonly referred to as andquot triple negative breast cancer andquotAs suchthe available treatments for breast cancer targeting these receptors do not work for TNBC patientsTNBC distinguishes from other forms of breast cancer in tumor cell origination and progressionTNBC cells possess epithelialmesenchymal transition characteristics including invasionresistance to apoptosisand cancer stem cell like traits that permit tumor dissemination and growth at distant sitesRecentlywe discovered key transcription factors that are constitutively activated and sustain over expression of oncogenesenabling rapid growth and spreadmetastasisof TNBC tumorsOur new small molecule inhibitordesigned to block the transcription activities of these TNBC transcription factorseffectively blocks metastatic TNBC tumorigenesis in miceTo fully explore this unprecedented opportunity to develop safe and precision medicine against TNBCwe will accomplish two Specific Aims in the Phase I of this projectwhich are to develop highly potent and selective inhibitors that block triple negative breast cancer tumorigenesisand to simultaneously characterize our new epigenetic drug molecules as novel targeted therapeutic agents for TNBCThe Phase I results will prepare us for a more efficient Phase II study of an extensive pre clinical evaluation of our most promising drug candidates in future human clinical trials PUBLIC HEALTH RELEVANCETriple negative breast cancer is one of the most aggressive forms of human cancer and currently has no targeted therapyWe recently discovered a fundamental epigenetic disease mechanism that underlies tumor cell origination and progressiona distinct feature and a root cause of triple negative breast cancerIn this project we will explore the therapeutic potential of this new disease mechanism by establishing predictive molecular biomarkers and developing promising lead drug candidates for next extensive preclinical study of producing new targeted epigenetic medicine to fight against triplenegative breast cancer