Abstract B05: Self-assembling platinum-acridine loaded carbon nanotubes for triple-negative breast cancer chemotherapy

Triple-negative breast cancer (TNBC) accounts for 10-15% of breast cancers, has the highest levels of recurrence, and the lowest five-year survival of all breast cancer subtypes. TNBC does not express estrogen or progesterone receptors and does not overexpress HER2 receptors. Therefore, TNBC does not benefit from current FDA-approved targeted therapies against HER2 or hormone-positive cancers. Early clinical trials show that TNBC is susceptible to platinum chemotherapy, but dose-limiting toxicities and cross-resistance amongst current FDA-approved platinum agents may limit clinical efficacy. To address this issue, we have developed a novel drug delivery system consisting of a potent, non-classical platinum chemotherapeutic that self-assembles onto the surface of carbon nanotubes. Our pharmacophore, termed platinum-acridines (PA), is an anticancer agent composed of a platinum group modified with an acridine. The platinum-group of the PA functions to bind and platinate DNA, while the acridine group functions as a classical DNA intercalator. This coordination allows for platination of DNA near the intercalation site, leading to a more severe form of damage than the crosslinks induced by cisplatin which may increase potency and limit cross-resistance. Platinum-acridines show efficacy against breast cancer in vitro, but preclinical studies show a possibility of dose-limiting toxicities; thus PA may be most beneficial specifically delivered to the tumor using a nanocarrier such as ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research