노경희 (한국생명공학연구원, The University of Texas MD Anderson Cancer Center) | 한빛사논문 > 한빛사

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한국생명공학연구원, The University of Texas MD Anderson Cancer Center

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Nat. Commun., 2023 Apr 26;14(1):2407 | https://doi.org/10.1038/s41467-023-36910-5 Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L

Christopher J. LaFargue^1,23, Paola Amero ^2,3,23, Kyunghee Noh^1,4,23, Lingegowda S. Mangala^1,5, Yunfei Wen¹, Emine Bayraktar¹, Sujanitha Umamaheswaran¹, Elaine Stur1, Santosh K. Dasari¹, Cristina Ivan², Sunila Pradeep⁶, Wonbeak Yoo⁷, Chunhua Lu¹, Nicholas B. Jennings¹, Vinod Vathipadiekal^8,9, Wei Hu¹, Anca Chelariu-Raicu^1,10,11, Zhiqiang Ku¹², Hui Deng¹², Wei Xiong¹², Hyun-Jin Choi^13,14, Min Hu¹⁵, Takae Kiyama¹⁶, Chai-An Mao^16,17, Rouba Ali-Fehmi¹⁸, Michael J. Birrer¹⁹, Jinsong Liu²⁰, Ningyan Zhang¹², Gabriel Lopez-Berestein^2,5, Vittorio de Franciscis^21,22, Zhiqiang An¹²& Anil K. Sood^1,5

¹Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
²Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
³Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Naples, Italy.
⁴Laboratory of Disease Modeling and Therapeutics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
⁵Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
⁷Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁸Wave Life Sciences, 733 Concord Avenue, Cambridge, MA 02138, USA.
⁹Department of Genetic Medicines, Alloy Therapeutics, Waltham, USA.
¹⁰Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany.
¹¹German Cancer Consortium (DKTK), German Cancer Research Center, Munich, Germany.
¹²Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
¹³Department of Obstetrics and Gynecology, Chung-Ang University, College of Medicine, Seoul, Republic of Korea.
¹⁴Department of Obstetrics and Gynecology, Chung-Ang University Gwangmyeong Hospital, College of Medicine Chung-Ang University, Seoul, South Korea.
¹⁵CPRIT Single Core, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA.
¹⁷The MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
¹⁸Department of Pathology, Wayne State University, Detroit, MI 48201, USA.
¹⁹Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences, Little Rock, AR, USA.
²⁰Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
²¹National Research Council (CNR), Institute of Genetic and Biomedical Research (IRGB)-UOS Milan via Rita Levi Montalcini, 20090 Pieve Emanuele, MI, Italy.
²²Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02115, USA.
²³These authors contributed equally: Christopher J. LaFargue, Paola Amero, Kyunghee Noh.

Corresponding authors : Correspondence to Yunfei Wen or Anil K. Sood.

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.

논문정보

형식Research article
게재일2023년 04월 (BRIC 등록일 2023-04-29)
연구진국내+국외 연구진
분야 생명과학 > 노화/암생물학

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