This Small Business Research (SBIR) Phase I project tests the application of a thermally responsive biopolymer, simultaneously to deliver breast cancer therapy and to prevent disease recurrence. Encouraging responses to multimodal treatments (surgery, radiotherapy, chemotherapy) are too often followed by more aggressive and resistant breast cancers, attributed to cancer stem cell survival and proliferation, as regulated by the oncogenic role of Notch signaling. This Phase 1 project seeks: (1) to achieve targeted reduction of breast tumor stem cells during treatment through externally triggered delivery of potent chemotherapeutics via Notch signaling pathway inhibitory peptides that are optimized to selectively accumulate within breast tumors, (2) to evaluate in an established, in vivo mouse model of breast cancer this approach?s capacity to reduce breast tumors and spare healthy tissue, and (3) to identify, in a subpopulation of treated animals, the presence or absence of tumor recurrence over 5 months. The broad, commercial impact of this project lies in its technological potential to deliver a therapeutic peptide that targets and inhibits cancer stem cells, thereby boosting prevention of and lowering likelihood for cancer recurrence. Success in the proposed experiments would further indicate that this technology can be modified to achieve the targeted delivery of other highly specific anti-cancer drug that are designed to target any solid tumor, increasing treatment specificity and efficacy, while reducing cytotoxicity in normal tissues. It would further indicate that the technology can be modified for other diseases requiring targeted delivery of therapeutics. Immediately, however, cancer recurrences arising from triple-negative breast cancer are a rapidly increasing clinical problem. They are associated with poor prognosis and limited systemic therapeutic options, diminish gains achieved through current standard of breast cancer care and weigh heavily on patients in remission and strategies of their treatment team. Success in the proposed in vivo studies of the biopolymer could lead to clinical translation, commercialization, and most importantly greater effectiveness in initial cancer regimens, with greatly lessened likelihood of recurrence, of broad clinical and health care significance and impact.
