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用鞘脂激活蛋白C-二油酰磷脂酰丝氨酸纳米药物靶向升高的细胞表面磷脂酰丝氨酸作为胰腺癌的单独或联合治疗

Targeting of elevated cell surface phosphatidylserine with saposin C-dioleoylphosphatidylserine nanodrug as individual or combination therapy for pancreatic cancer.

作者信息

Davis Harold W, Kaynak Ahmet, Vallabhapurapu Subrahmanya D, Qi Xiaoyang

机构信息

Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Brain Tumor Center at UC Neuroscience Institute, Cincinnati, OH 45267, United States.

出版信息

World J Gastrointest Oncol. 2021 Jun 15;13(6):550-559. doi: 10.4251/wjgo.v13.i6.550.

Abstract

Pancreatic cancer is one of the deadliest of cancers with a five-year survival of roughly 8%. Current therapies are: surgery, radiation and chemotherapy. Surgery is curative only if the cancer is caught very early, which is rare, and the latter two modalities are only marginally effective and have significant side effects. We have developed a nanosome comprised of the lysosomal protein, saposin C (SapC) and the acidic phospholipid, dioleoylphosphatidylserine (DOPS). In the acidic tumor microenvironment, this molecule, SapC-DOPS, targets the phosphatidylserine cancer-biomarker which is predominantly elevated on the surface of cancer cells. Importantly, SapC-DOPS can selectively target pancreatic tumors and metastases. Furthermore, SapC-DOPS has exhibited an impressive safety profile with only a few minor side effects in both preclinical experiments and in phase I clinical trials. With the dismal outcomes for pancreatic cancer there is an urgent need for better treatments and SapC-DOPS is a good candidate for addition to the oncologist's toolbox.

摘要

胰腺癌是最致命的癌症之一,五年生存率约为8%。目前的治疗方法有:手术、放疗和化疗。只有在癌症极早期被发现时,手术才有治愈可能,但这种情况很罕见,而后两种治疗方式效果甚微且有明显副作用。我们研发了一种纳米体,它由溶酶体蛋白鞘脂激活蛋白C(SapC)和酸性磷脂二油酰磷脂酰丝氨酸(DOPS)组成。在酸性肿瘤微环境中,这种分子SapC-DOPS靶向磷脂酰丝氨酸这种癌症生物标志物,其在癌细胞表面的水平通常会升高。重要的是,SapC-DOPS能选择性地靶向胰腺肿瘤和转移灶。此外,在临床前实验和I期临床试验中,SapC-DOPS都显示出令人印象深刻的安全性,仅有一些轻微副作用。鉴于胰腺癌的预后不佳,迫切需要更好的治疗方法,而SapC-DOPS是肿瘤学家治疗手段中的一个不错候选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c76e/8204355/0057fa696d5b/WJGO-13-550-g001.jpg

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