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通过靶向 CD5L 克服抗 VEGF 治疗的适应性耐药。

Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L.

机构信息

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

出版信息

Nat Commun. 2023 Apr 26;14(1):2407. doi: 10.1038/s41467-023-36910-5.

DOI:10.1038/s41467-023-36910-5
PMID:37100807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10133315/
Abstract

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility.

摘要

抗血管内皮生长因子 (VEGF) 途径的血管生成治疗是对抗肿瘤生长和进展的有力工具；然而，耐药性经常出现。我们确定 CD5L（CD5 抗原样前体）作为一种重要的基因，在抗血管生成治疗后上调，导致适应性耐药的出现。通过使用针对 CD5L 的 RNA-适体和单克隆抗体，我们能够减轻 CD5L 过表达在体外和体内环境中的促血管生成作用。此外，我们发现癌症患者血管 CD5L 的表达增加与贝伐单抗耐药和总体生存率降低有关。这些发现表明 CD5L 是对血管生成治疗产生适应性耐药的一个重要因素，并表明靶向 CD5L 的方法具有潜在的重要临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/3265634e3de3/41467_2023_36910_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/9f0c822c3616/41467_2023_36910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/444dfd6f5509/41467_2023_36910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/f7bee20829a2/41467_2023_36910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/41c971af2e45/41467_2023_36910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/d453ab2ff570/41467_2023_36910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/9794e0e26fac/41467_2023_36910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/0b894b30dfef/41467_2023_36910_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/3265634e3de3/41467_2023_36910_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/9f0c822c3616/41467_2023_36910_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/444dfd6f5509/41467_2023_36910_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/f7bee20829a2/41467_2023_36910_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/41c971af2e45/41467_2023_36910_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/d453ab2ff570/41467_2023_36910_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/9794e0e26fac/41467_2023_36910_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/0b894b30dfef/41467_2023_36910_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0363/10133315/3265634e3de3/41467_2023_36910_Fig8_HTML.jpg

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