Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L. Nat Commun 2023 Apr 26;14(1):2407
Date
04/27/2023Pubmed ID
37100807Pubmed Central ID
PMC10133315DOI
10.1038/s41467-023-36910-5Scopus ID
2-s2.0-85153918496 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
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 List
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 AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAntibodies, Monoclonal
Apoptosis Regulatory Proteins
Bevacizumab
Humans
Neoplasms
Receptors, Scavenger
Vascular Endothelial Growth Factor A
