Nature Communications (Apr 2023)
Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L
- Christopher J. LaFargue,
- Paola Amero,
- Kyunghee Noh,
- Lingegowda S. Mangala,
- Yunfei Wen,
- Emine Bayraktar,
- Sujanitha Umamaheswaran,
- Elaine Stur,
- Santosh K. Dasari,
- Cristina Ivan,
- Sunila Pradeep,
- Wonbeak Yoo,
- Chunhua Lu,
- Nicholas B. Jennings,
- Vinod Vathipadiekal,
- Wei Hu,
- Anca Chelariu-Raicu,
- Zhiqiang Ku,
- Hui Deng,
- Wei Xiong,
- Hyun-Jin Choi,
- Min Hu,
- Takae Kiyama,
- Chai-An Mao,
- Rouba Ali-Fehmi,
- Michael J. Birrer,
- Jinsong Liu,
- Ningyan Zhang,
- Gabriel Lopez-Berestein,
- Vittorio de Franciscis,
- Zhiqiang An,
- Anil K. Sood
Affiliations
- Christopher J. LaFargue
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Paola Amero
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center
- Kyunghee Noh
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Lingegowda S. Mangala
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Yunfei Wen
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Emine Bayraktar
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Sujanitha Umamaheswaran
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Elaine Stur
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Santosh K. Dasari
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Cristina Ivan
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center
- Sunila Pradeep
- Department of Obstetrics and Gynecology, Medical College of Wisconsin
- Wonbeak Yoo
- Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center
- Chunhua Lu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Nicholas B. Jennings
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Vinod Vathipadiekal
- Wave Life Sciences
- Wei Hu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Anca Chelariu-Raicu
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Zhiqiang Ku
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston
- Hui Deng
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston
- Wei Xiong
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston
- Hyun-Jin Choi
- Department of Obstetrics and Gynecology, Chung-Ang University, College of Medicine
- Min Hu
- CPRIT Single Core, Department of Genetics, The University of Texas MD Anderson Cancer Center
- Takae Kiyama
- Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth)
- Chai-An Mao
- Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth)
- Rouba Ali-Fehmi
- Department of Pathology, Wayne State University
- Michael J. Birrer
- Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences
- Jinsong Liu
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- Ningyan Zhang
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston
- Gabriel Lopez-Berestein
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center
- Vittorio de Franciscis
- National Research Council (CNR), Institute of Genetic and Biomedical Research (IRGB)-UOS Milan via Rita Levi Montalcini
- Zhiqiang An
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston
- Anil K. Sood
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-023-36910-5
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
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.
