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纳米治疗药物的组合方法在前列腺癌炎症通路靶向治疗中的应用。

Combinatorial approaches of nanotherapeutics for inflammatory pathway targeted therapy of prostate cancer.

机构信息

Polymer Nanobiomaterial Research Laboratory, Nanoscience and Microfluidics Division, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka 575018, India.

Cell Signaling and Cancer Biology Division, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka 575018, India.

出版信息

Drug Resist Updat. 2022 Sep;64:100865. doi: 10.1016/j.drup.2022.100865. Epub 2022 Sep 7.

Abstract

Prostate cancer (PC) is the most prevalent male urogenital cancer worldwide. PC patients presenting an advanced or metastatic cancer succumb to the disease, even after therapeutic interventions including radiotherapy, surgery, androgen deprivation therapy (ADT), and chemotherapy. One of the hallmarks of PC is evading immune surveillance and chronic inflammation, which is a major challenge towards designing effective therapeutic formulations against PC. Chronic inflammation in PC is often characterized by tumor microenvironment alterations, epithelial-mesenchymal transition and extracellular matrix modifications. The inflammatory events are modulated by reactive nitrogen and oxygen species, inflammatory cytokines and chemokines. Major signaling pathways in PC includes androgen receptor, PI3K and NF-κB pathways and targeting these inter-linked pathways poses a major therapeutic challenge. Notably, many conventional treatments are clinically unsuccessful, due to lack of targetability and poor bioavailability of the therapeutics, untoward toxicity and multidrug resistance. The past decade witnessed an advancement of nanotechnology as an excellent therapeutic paradigm for PC therapy. Modern nanovectorization strategies such as stimuli-responsive and active PC targeting carriers offer controlled release patterns and superior anti-cancer effects. The current review initially describes the classification, inflammatory triggers and major inflammatory pathways of PC, various PC treatment strategies and their limitations. Subsequently, recent advancement in combinatorial nanotherapeutic approaches, which target PC inflammatory pathways, and the mechanism of action are discussed. Besides, the current clinical status and prospects of PC homing nanovectorization, and major challenges to be addressed towards the advancement PC therapy are also addressed.

摘要

前列腺癌(PC)是全球最常见的男性泌尿生殖系统癌症。即使在包括放疗、手术、雄激素剥夺疗法(ADT)和化疗在内的治疗干预后,患有晚期或转移性癌症的 PC 患者仍会死于该疾病。PC 的标志之一是逃避免疫监视和慢性炎症,这是针对 PC 设计有效治疗制剂的主要挑战。PC 中的慢性炎症通常表现为肿瘤微环境改变、上皮-间充质转化和细胞外基质修饰。炎症事件受活性氮和氧物种、炎症细胞因子和趋化因子的调节。PC 中的主要信号通路包括雄激素受体、PI3K 和 NF-κB 通路,针对这些相互关联的通路是一个主要的治疗挑战。值得注意的是,由于缺乏治疗靶点的靶向性和生物利用度、不良毒性和多药耐药性,许多传统治疗在临床上都不成功。过去十年见证了纳米技术作为 PC 治疗的一种极好的治疗范例的进步。现代纳米载体化策略,如刺激响应和主动 PC 靶向载体,提供了控制释放模式和卓越的抗癌效果。目前的综述首先描述了 PC 的分类、炎症触发因素和主要炎症通路、各种 PC 治疗策略及其局限性。随后,讨论了针对 PC 炎症通路的组合纳米治疗方法的最新进展及其作用机制。此外,还讨论了 PC 归巢纳米载体化的当前临床状况和前景,以及针对 PC 治疗进展需要解决的主要挑战。

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