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Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L

Author

Listed:
  • Christopher J. LaFargue

    (The University of Texas MD Anderson Cancer Center)

  • Paola Amero

    (The University of Texas MD Anderson Cancer Center
    Istituto di Endocrinologia ed Oncologia Sperimentale, CNR)

  • Kyunghee Noh

    (The University of Texas MD Anderson Cancer Center
    Korea Research Institute of Bioscience and Biotechnology)

  • Lingegowda S. Mangala

    (The University of Texas MD Anderson Cancer Center
    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
    Alloy Therapeutics)

  • Wei Hu

    (The University of Texas MD Anderson Cancer Center)

  • Anca Chelariu-Raicu

    (The University of Texas MD Anderson Cancer Center
    Ludwig Maximilians University of Munich
    German Cancer Research 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
    Chung-Ang University Gwangmyeong Hospital, College of Medicine Chung-Ang University)

  • 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)
    The MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences)

  • 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
    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
    Harvard Medical School Initiative for RNA Medicine, Harvard Medical School)

  • Zhiqiang An

    (The University of Texas Health Science Center at Houston)

  • Anil K. Sood

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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, 2023. "Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36910-5
    DOI: 10.1038/s41467-023-36910-5
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