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Additional file 1: Figure S1. Study diagram. Figure S2. Incidence of grade 3 diarrhea during neoadjuvant treatment. Table S1. Clinical responses following neoadjuvant treatment assessed by local investigator per RECIST v1.1. Table S2. Exposure of the individual components of study treatment. Table S3. Serious adverse events during neoadjuvant therapy. Table S4. Summary of data on diarrhea during neoadjuvant treatment. Table S5. Characteristics of diarrhea before and after proactive management. Table S6. Overview of neutropenia, febrile neutropenia, and decreased white blood cell count during neoadjuvant treatment period.

Multidrug resistance (MDR) remains one of major limitation for the successful treatment of many cancers including breast cancer. Co-delivery of chemotherapeutic drugs and small interfering RNA (siRNA) has been developed because of its ability to generate synergistic anticancer effects via different mechanisms of action, to reverse MDR and increase the efficacy of chemotherapeutic drugs in cancer therapy. Herein, we employed a kind of efficient multifunctional tumor targeted nanomicelles (PECL3) for the co-delivery of hydrophobic anti-cancer drugs and siRNA. This kind of nanomicelles were constructed by folic acid (FA)-decorated PEG-b-(PCL-g-PEI)-b-PCL triblock copolymers, which were synthesized through "click chemistry" and "ring opening" polymerization. Driven by the "core-shell" structure and the electrostatic interaction, this triblock copolymer could efficiently encapsulate P-glycoprotein (P-gp) siRNA and doxorubicin (DOX). The obtained nanomicelles can prevent renal clearance, RNase degradation and aggregation in circulation. Compared to the non-specific delivery, these FA functionalized nanomicelles could efficiently deliver P-gp siRNA to reducing both P-gp expression levels and IC50 value of the DOX in DOX-resistant breast cancer cells (MCF-7/ADR). Additionally, in vivo results showed that DOX loaded PECL3 (D-PECL3) micelles could reduce toxicity of DOX on nontarget tissues and significantly inhibited MCF-7/ADR tumor growth through encapsulating DOX in the micelles and deliver them to target tumor region. Taken together, these results proof that PECL3 micelles could co-deliver siRNA and drug to inhibit MDR tumor growth. These results suggested that the co-delivery of DOX and siRNA in tumor-targeting nanomicelles could excite synergistic effect of gene therapy and chemotherapy, thus can efficiently reverse MDR cancer and kill the cancer cells.

DKK1 is a secreted glycoprotein that inhibits Wnt/β-catenin signaling but may up-regulate the nonconanical Wnt signaling. Consistent with its inhibitory function in Wnt/β-catenin signaling, aberrant DKK1 expression has been observed in many types of human cancers, while contradicting findings have been reported in other studies. There are also several studies on serum DKK1 levels in various cancers with conflicting findings. In the present study, serum DKK1 was determined in 217 non- small cell lung cancer (NSCLC) patients, 35 small cell lung cancer (SCLC) patients and 286 matched healthy controls using a commercially available ELISA assay kit. Compared to healthy controls, serum DKK1 level was significantly lower in NSCLC (p < 10-28) and SCLC (p