Specificity and safety of a targeted therapy against triple negative breast cancer

PROJECT SUMMARY ABSTRACT Despite recent advances in the treatment of breast cancerBCthere is a pressing unmet medical need as BC remains the second leading cause of cancer related deaths among womenInnovative new approaches are especially needed to help patients with triple negative BCTNBCas TNBCandapos s inherently aggressive clinical behavior and the lack of recognized molecular targets for therapy leads to a poorer outcomeThe goal of this phase I application is to validate a high affinity inhibitor of the transcription factor RUNXwhich has great promise to be a game changer in the treatment of BCincluding TNBCRUNXis a validated target for breast cancer that is expressed in luminaltriple negativeTNBCas well as HERBCIts expression is associated with poor survival and its mechanism of action is well understoodWe have used computer assisted drug design to identify our lead compound CADDCADDbinds with high affinity to the DNA binding pocket of the RUNXDNA binding domainand we have shown it to inhibit DNA bindingcell proliferationtranscriptional activityand tumor growthThe successful development of CADDinto the clinic will fill the significant unmet medical need for patients with metastatic BCThis application describes the work necessary to complete preclinical developmentand will position CADDfor accelerated development in the clinicThroughout this SBIR Phase Iwe will also evaluate opportunities to bring in collaborators with drug development expertiseWe have already obtained support from Daiichi Sankyosee lettera leader in the development of new oncology therapiesThe data obtained in this SBIR will be both essential and sufficient to reach the milestones that are needed to garner the support from drug development organizations that can advance our strategy intoand throughthe clinic PROJECT NARRATIVE Despite recent advances in the treatment breast cancerBCthere is a pressing unmet medical need as BC remains the second leading cause of cancer related deaths among womenInnovative new approaches are especially needed to help patients with triple negative BCTNBCas TNBCandapos s inherently aggressive clinical behavior and the lack of recognized molecular targets for therapy leads to a poorer outcomeThe goal of this work is to begin development of a molecule which has great promise to be a game changer in the treatment of BCincluding TNBC