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 Franciscis, Zhiqiang An and Anil K. Sood ()
Additional contact information
Christopher J. LaFargue: The University of Texas MD Anderson Cancer Center
Paola Amero: The University of Texas MD Anderson Cancer Center
Kyunghee Noh: The University of Texas MD Anderson Cancer Center
Lingegowda S. Mangala: The University of Texas MD Anderson Cancer Center
Yunfei Wen: The University of Texas MD Anderson Cancer Center
Emine Bayraktar: The University of Texas MD Anderson Cancer Center
Sujanitha Umamaheswaran: The University of Texas MD Anderson Cancer Center
Elaine Stur: The University of Texas MD Anderson Cancer Center
Santosh K. Dasari: The University of Texas MD Anderson Cancer Center
Cristina Ivan: The University of Texas MD Anderson Cancer Center
Sunila Pradeep: Medical College of Wisconsin
Wonbeak Yoo: The University of Texas MD Anderson Cancer Center
Chunhua Lu: The University of Texas MD Anderson Cancer Center
Nicholas B. Jennings: The University of Texas MD Anderson Cancer Center
Vinod Vathipadiekal: Wave Life Sciences
Wei Hu: The University of Texas MD Anderson Cancer Center
Anca Chelariu-Raicu: The University of Texas MD Anderson Cancer Center
Zhiqiang Ku: The University of Texas Health Science Center at Houston
Hui Deng: The University of Texas Health Science Center at Houston
Wei Xiong: The University of Texas Health Science Center at Houston
Hyun-Jin Choi: Chung-Ang University, College of Medicine
Min Hu: The University of Texas MD Anderson Cancer Center
Takae Kiyama: McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth)
Chai-An Mao: McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth)
Rouba Ali-Fehmi: Wayne State University
Michael J. Birrer: Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences
Jinsong Liu: The University of Texas MD Anderson Cancer Center
Ningyan Zhang: The University of Texas Health Science Center at Houston
Gabriel Lopez-Berestein: The University of Texas MD Anderson Cancer Center
Vittorio Franciscis: National Research Council (CNR), Institute of Genetic and Biomedical Research (IRGB)-UOS Milan via Rita Levi Montalcini
Zhiqiang An: The University of Texas Health Science Center at Houston
Anil K. Sood: The University of Texas MD Anderson Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 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.

Date: 2023
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DOI: 10.1038/s41467-023-36910-5

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