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

Autor: LaFargue CJ; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Amero P; 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., Noh K; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.; Laboratory of Disease Modeling and Therapeutics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea., Mangala LS; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Wen Y; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. ywen2@mdanderson.org., Bayraktar E; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Umamaheswaran S; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Stur E; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Dasari SK; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Ivan C; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Pradeep S; Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Yoo W; Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Lu C; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Jennings NB; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Vathipadiekal V; Wave Life Sciences, 733 Concord Avenue, Cambridge, MA, 02138, USA.; Department of Genetic Medicines, Alloy Therapeutics, Waltham, USA., Hu W; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA., Chelariu-Raicu A; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.; Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center, Munich, Germany., Ku Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Deng H; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Xiong W; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Choi HJ; 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., Hu M; CPRIT Single Core, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Kiyama T; 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., Mao CA; 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., Ali-Fehmi R; Department of Pathology, Wayne State University, Detroit, MI, 48201, USA., Birrer MJ; Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences, Little Rock, AR, USA., Liu J; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Zhang N; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Lopez-Berestein G; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., de Franciscis V; 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., An Z; Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Sood AK; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. asood@mdanderson.org.; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. asood@mdanderson.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 26; Vol. 14 (1), pp. 2407. Date of Electronic Publication: 2023 Apr 26.
DOI: 10.1038/s41467-023-36910-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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