Targeted Small Molecular Mertansine Delivery for Triple Negative Breast Cancer Treatment

Project Summary Triple negative breast cancerTNBCis a subtype of breast cancerthat occurs in aboutof diagnosed breast cancerswhich is more likely to affect younger peopleAfrican AmericansHispanicsand or those with BRCAgene mutationThe projected TNBC annually diagnosed cases in United States are estimated to be more thanbyDue to the lack of the identified receptors on tumor cell surfaceTNBC patients cannot benefit from targeted hormone therapies or anti HERtreatments and have the worst prognosis among all types of breast cancerThis Small Business Innovation Research project proposes to develop a novel targeting technology named Active Tissue Targeting via Anchored ClicK ChemistryATTACKfor targeted TNBC treatmentCompared to conventional targeting technologies such as antibodiesthe small molecule based tumor labeling and targeting strategy can potentially treatment antibodyuntargetablecancers such as TNBCThe strategy represents a new generation cancer targeting technology for therapeutic drug deliveryThe ATTACK includes two agentsan azide containing sugar that can selective label cancer cells through cancer specific trigger reaction and metabolizationan azide targeting drug to selectively recognize the sugar labeled cancer cellsaccumulate preferentially in tumors and achieve therapeutic effectThe proposed Phase I study will demonstrate the feasibility of combining the azide containing sugar with a designed azide targeting drug for in vivo treatment of TNBC in murine tumor modelsPreliminary DMPK study will also be conducted to further validate the potential of the drug candidate Narrative We aim to develop a targeting technology for improved triple negative breast cancer treatmentThis proposed study introduces a small molecule based method to deliver mertansine conjugate selectively to triple negative breast tumors to achieve better efficacy and lower side effect