Triple-negative breast cancer (TNBC) is a subtype of breast cancer, that occurs in about 10-20% of diagnosed breast cancers, which is more likely to affect younger people, African Americans, Hispanics, and/or those with BRCA1 gene mutation. The projected TNBC annually diagnosed cases in United States are estimated to be more than 500,000 by 2020. Due to the lack of the identified receptors on tumor cell surface, TNBC patients cannot benefit from targeted hormone therapies or anti-HER2 treatments and have the worst prognosis among all types of breast cancer. This Small Business Innovation Research project proposes to develop a novel targeting technology named Active Tissue Targeting via Anchored ClicK Chemistry (ATTACK) for targeted TNBC treatment. Compared to conventional targeting technologies such as antibodies, the small molecule based tumor labeling and targeting strategy can potentially treatment antibody ?untargetable? cancers such as TNBC. The strategy represents a new generation cancer targeting technology for therapeutic drug delivery. The ATTACK includes two agents: 1) an azide-containing sugar that can selective label cancer cells through cancer-specific trigger reaction and metabolization; 2) an azide-targeting drug to selectively recognize the sugar labeled cancer cells, accumulate preferentially in tumors and achieve therapeutic effect. The 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 models. Preliminary DMPK study will also be conducted to further validate the potential of the drug candidate.
We aim to develop a targeting technology for improved triple negative breast cancer treatment. This 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.
