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

doi:10.1038/s41467-023-36910-5

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 XiongHyun 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

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	2407
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36910-5
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

MD Anderson CCSG core facilities

Research Animal Support Facility
Cytogenetics and Cell Authentication Core
Advanced Technology Genomics Core
Functional Proteomics Reverse Phase Protein Array Core
Bioinformatics Shared Resource
Flow Cytometry and Cellular Imaging Facility

Access to Document

10.1038/s41467-023-36910-5

Cite this

LaFargue, C. J., Amero, P., Noh, K., Mangala, L. S., Wen, Y., Bayraktar, E., Umamaheswaran, S., Stur, E., Dasari, S. K., Ivan, C., Pradeep, S., Yoo, W., Lu, C., Jennings, N. B., Vathipadiekal, V., Hu, W., Chelariu-Raicu, A., Ku, Z., Deng, H., ... Sood, A. K. (2023). Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L. Nature communications, 14(1), Article 2407. https://doi.org/10.1038/s41467-023-36910-5

LaFargue, CJ, Amero, P, Noh, K, Mangala, LS , Wen, Y, Bayraktar, E, Umamaheswaran, S, Stur, E, Dasari, SK, Ivan, C, Pradeep, S, Yoo, W, Lu, C, Jennings, NB, Vathipadiekal, V, Hu, W, Chelariu-Raicu, A, Ku, Z, Deng, H, Xiong, W, Choi, HJ, Hu, M, Kiyama, T, Mao, CA, Ali-Fehmi, R, Birrer, MJ, Liu, J, Zhang, N, Lopez-Berestein, G, de Franciscis, V, An, Z & Sood, AK 2023, 'Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L', Nature communications, vol. 14, no. 1, 2407. https://doi.org/10.1038/s41467-023-36910-5

@article{5bf7be968c3e4e8d9bea0c11da12a22f,

title = "Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L",

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.",

author = "LaFargue, {Christopher J.} and Paola Amero and Kyunghee Noh and Mangala, {Lingegowda S.} and Yunfei Wen and Emine Bayraktar and Sujanitha Umamaheswaran and Elaine Stur and Dasari, {Santosh K.} and Cristina Ivan and Sunila Pradeep and Wonbeak Yoo and Chunhua Lu and Jennings, {Nicholas B.} and Vinod Vathipadiekal and Wei Hu and Anca Chelariu-Raicu and Zhiqiang Ku and Hui Deng and Wei Xiong and Choi, {Hyun Jin} and Min Hu and Takae Kiyama and Mao, {Chai An} and Rouba Ali-Fehmi and Birrer, {Michael J.} and Jinsong Liu and Ningyan Zhang and Gabriel Lopez-Berestein and {de Franciscis}, Vittorio and Zhiqiang An and Sood, {Anil K.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-36910-5",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L

AU - LaFargue, Christopher J.

AU - Amero, Paola

AU - Noh, Kyunghee

AU - Mangala, Lingegowda S.

AU - Wen, Yunfei

AU - Bayraktar, Emine

AU - Umamaheswaran, Sujanitha

AU - Stur, Elaine

AU - Dasari, Santosh K.

AU - Ivan, Cristina

AU - Pradeep, Sunila

AU - Yoo, Wonbeak

AU - Lu, Chunhua

AU - Jennings, Nicholas B.

AU - Vathipadiekal, Vinod

AU - Hu, Wei

AU - Chelariu-Raicu, Anca

AU - Ku, Zhiqiang

AU - Deng, Hui

AU - Xiong, Wei

AU - Choi, Hyun Jin

AU - Hu, Min

AU - Kiyama, Takae

AU - Mao, Chai An

AU - Ali-Fehmi, Rouba

AU - Birrer, Michael J.

AU - Liu, Jinsong

AU - Zhang, Ningyan

AU - Lopez-Berestein, Gabriel

AU - de Franciscis, Vittorio

AU - An, Zhiqiang

AU - Sood, Anil K.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85153918496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85153918496&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-36910-5

DO - 10.1038/s41467-023-36910-5

M3 - Article

C2 - 37100807

AN - SCOPUS:85153918496

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2407

ER -

Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

Other files and links

Fingerprint

Cite this