紫杉醇、紫杉醇胶束和PARP抑制剂对三阴性乳腺癌肠道菌群的影响及疗效对比

The Impact of Paclitaxel, Paclitaxel Micelles, and PARP Inhibitors on the Gut Microbiota of Triple-Negative Breast Cancer and a Comparative Analysis of Their Therapeutic Efficacy

摘要: 三阴性乳腺癌是一种乳腺癌的亚型，其特点是缺乏雌激素受体、孕激素受体以及人表皮生长因子受体2 (HER2)受体的表达。这种癌症亚型对传统的内分泌治疗和HER2靶向治疗不敏感，因此对于三阴性乳腺癌的治疗仍然存在较大的挑战。紫杉醇是一种经典的癌症治疗药物，被广泛应用于三阴性乳腺癌的治疗中。然而，紫杉醇的疗效存在一定的局限性，其不良反应主要包括胃肠道反应、神经系统反应和骨髓抑制等。近年来，人们对于药物载体技术的研究成果日益丰富，其中胶束技术作为一种有效的药物传递系统，被广泛关注。紫杉醇胶束作为一种新型的紫杉醇制剂，具有较小的粒径、长时间的血药浓度稳定性以及较好的组织分布性。因此，探究紫杉醇胶束在治疗三阴性乳腺癌中的疗效以及对肠道菌群的影响具有重要的临床意义。此外，PARP抑制剂是一类针对DNA修复途径的药物，近年来被广泛用于治疗BRCA突变相关的乳腺癌。然而，目前关于PARP抑制剂在治疗三阴性乳腺癌中的作用还存在争议，并且其对肠道菌群的影响尚不清楚。因此，本研究旨在探究紫杉醇、紫杉醇胶束、紫杉醇加PARP抑制剂以及紫杉醇胶束加PARP抑制剂对三阴性乳腺癌肠道菌群的影响以及其疗效的对比。

Abstract: Triple-negative breast cancer constitutes a distinct subtype characterized by the conspicuous absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) expression. This variant, refractory to conventional endocrine therapy and HER2-targeted interventions, presents formidable challenges in clinical management. Paclitaxel, a venerable anti-neoplastic agent, has achieved pervasive utilization in the therapeutic landscape of triple-negative breast cancer. Nonetheless, the efficacy of paclitaxel confronts certain constraints, notably adverse reactions manifesting predominantly as gastrointestinal responses, neurological manifestations, and bone marrow suppression. Recent years have witnessed notable strides in drug delivery technologies, with a particular focus on the burgeoning domain of drug carrier systems. Micelle technology, distinguished as an efficacious drug delivery system, has undergone thorough exploration. Paclitaxel micelles, a novel formulation of the aforementioned agent, showcase reduced particle size, protracted stability in blood drug concentrations, and enhanced tissue distribution. Consequently, a profound inquiry into the efficacy of paclitaxel micelles in the treatment of triple-negative breast cancer and their ramifications on the intestinal microbiota assumes paramount clinical significance. Moreover, poly (ADP-ribose) polymerase (PARP) inhibitors emerge as a pharmacotherapeutic class targeting the DNA repair pathway, garnering widespread employment in the recent management of breast cancer associated with BRCA mutations. However, ongoing discussions regarding the role of PARP inhibitors in the treatment of triple-negative breast cancer remain contentious, and their impact on the intestinal microbiota remains enigmatic. Thus, this study endeavors to elucidate the effects on the intestinal microbiota and juxtapose the efficacy of paclitaxel, paclitaxel micelles, paclitaxel with PARP inhibitors, and paclitaxel micelles with PARP inhibitors in the context of triple-negative breast cancer.