<br>通过靶向 CD5L 克服抗 VEGF 治疗的适应性耐药,Nature Communications

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通过靶向 CD5L 克服抗 VEGF 治疗的适应性耐药
Nature Communications ( IF 14.7 ) Pub Date : 2023-04-26 , DOI: 10.1038/s41467-023-36910-5
Christopher J LaFargue ₁ , Paola Amero _{2,

3} , Kyunghee Noh _{1,

4} , Lingegowda S Mangala _{1,

5} , Yunfei Wen ₁ , Emine Bayraktar ₁ , Sujanitha Umamaheswaran ₁ , Elaine Stur ₁ , Santosh K Dasari ₁ , Cristina Ivan ₂ , Sunila Pradeep ₆ , Wonbeak Yoo ₇ , Chunhua Lu ₁ , Nicholas B Jennings ₁ , Vinod Vathipadiekal _{8,

9} , Wei Hu ₁ , Anca Chelariu-Raicu _{1,

10,

11} , Zhiqiang Ku ₁₂ , Hui Deng ₁₂ , Wei Xiong ₁₂ , Hyun-Jin Choi _{13,

14} , Min Hu ₁₅ , Takae Kiyama ₁₆ , Chai-An Mao _{16,

17} , Rouba Ali-Fehmi ₁₈ , Michael J Birrer ₁₉ , Jinsong Liu ₂₀ , Ningyan Zhang ₁₂ , Gabriel Lopez-Berestein _{2,

5} , Vittorio de Franciscis _{21,

22} , Zhiqiang An ₁₂ , Anil K Sood _{1,

5}

Affiliation

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.
Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy.
Laboratory of Disease Modeling and Therapeutics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Wave Life Sciences, 733 Concord Avenue, Cambridge, MA, 02138, USA.
Department of Genetic Medicines, Alloy Therapeutics, Waltham, USA.
Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center, Munich, Germany.
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Department of Obstetrics and Gynecology, Chung-Ang University, College of Medicine, Seoul, Republic of Korea.
Department of Obstetrics and Gynecology, Chung-Ang University Gwangmyeong Hospital, College of Medicine Chung-Ang University, Seoul, South Korea.
CPRIT Single Core, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, 77030, USA.
The MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, Houston, TX, 77030, USA.
Department of Pathology, Wayne State University, Detroit, MI, 48201, USA.
Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
National Research Council (CNR), Institute of Genetic and Biomedical Research (IRGB)-UOS Milan via Rita Levi Montalcini, 20090, Pieve Emanuele, MI, Italy.
Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA, 02115, USA.

针对血管内皮生长因子（VEGF）途径的抗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。我们将 CD5L（CD5 抗原样前体）确定为响应抗血管生成治疗而上调的重要基因，导致适应性耐药的出现。通过使用 RNA 适体和靶向 CD5L 的单克隆抗体，我们能够在体外和体内环境中减弱 CD5L 过度表达的促血管生成作用。此外，我们发现癌症患者血管 CD5L 表达增加与贝伐单抗耐药性和较差的总生存期相关。这些发现表明 CD5L 是对抗血管生成治疗适应性抵抗的重要因素，并表明靶向 CD5L 的方式具有潜在的重要临床实用性。

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更新日期：2023-04-27

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