Nanoparticles Loaded with Wnt and YAP/Mevalonate Inhibitors in Combination with Paclitaxel Stop the Growth of TNBC Patient‐Derived Xenografts and Diminish Tumorigenesis

• DOI: 10.1002/adtp.202000123
• Publication Date: 2020-08-13T08:47:59Z
• Authors: Andrew Sulaiman; Sarah McGarry; Sara El‐Sahli; Li Li; Jason Chambers; Alexandra Phan; Emil Al‐Kadi; Zaina Kahiel; Eliya Farah; Guang Ji; Seung‐Hwan Lee; Krishna K. Inampudi; Tommy Alain; Xuguang Li; Sheng Liu; Xianghui Han; Peiyong Zheng; Zhen Liu; Suresh Gadde; Lisheng Wang
• Keywords: Triple-negative breast cancer

Abstract Triple negative breast cancer (TNBC) accounts for the majority of cancer‐related deaths and remains hardest to treat due lack specific therapeutic targets. While chemotherapy is mainstay systemic treatment TNBC, it associated with chemotherapy‐induced stem cells (CSCs) tumor regeneration. Here, found that Wnt YAP target genes have been closely CSCs are highly expressed in TNBC patient tumors negatively correlated survival. Therefore, a nanotherapeutic strategy employed, using nanomaterials approved by FDA, two co‐delivery nanoparticle platforms (NPs) developed TNBC. These NPs contain inhibitor PRI‐724 (in clinical trials) YAP/mevalonate simvastatin (FDA‐approved). Toward translation, efficacy assessed clinically relevant patient‐derived xenograft (PDX) models. combination chemotherapeutic drug paclitaxel effectively halt growth both paclitaxel‐resistant paclitaxel‐sensitive PDX tumors, diminish paclitaxel‐induced CSC enrichment around fourfold. Importantly, also decrease paclitaxel‐enhanced tumorigenesis after secondary transplantation. Together, this study demonstrates NP translatable models, suggesting their application potential