PUBLICATION
Connective tissue growth factor contributes to resistance to anti-angiogenic therapies in renal cancer
- Authors
- Teisseire, M., Karaulic, A., Parola, J., Totobesola, M., Borchiellini, D., Pace-Loscos, T., Schiappa, R., Chamorey, E., Durivault, J., Dufies, M., Ambrosetti, D., Luciano, F., Gao, J., Cao, Y., Pagès, G., Giuliano, S.
- ID
- ZDB-PUB-260310-2
- Date
- 2026
- Source
- Theranostics 16: 448945074489-4507 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors*/pharmacology
- Angiogenesis Inhibitors*/therapeutic use
- Animals
- Axitinib/pharmacology
- Carcinoma, Renal Cell*/drug therapy
- Carcinoma, Renal Cell*/genetics
- Carcinoma, Renal Cell*/metabolism
- Carcinoma, Renal Cell*/pathology
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Connective Tissue Growth Factor*/blood
- Connective Tissue Growth Factor*/genetics
- Connective Tissue Growth Factor*/metabolism
- Drug Resistance, Neoplasm*/genetics
- Female
- Gene Expression Regulation, Neoplastic/drug effects
- Humans
- Kidney Neoplasms*/drug therapy
- Kidney Neoplasms*/genetics
- Kidney Neoplasms*/metabolism
- Kidney Neoplasms*/pathology
- Male
- Neovascularization, Pathologic/drug therapy
- Proteomics
- Sunitinib/pharmacology
- Zebrafish
- PubMed
- 41799185 Full text @ Theranostics
Citation
Teisseire, M., Karaulic, A., Parola, J., Totobesola, M., Borchiellini, D., Pace-Loscos, T., Schiappa, R., Chamorey, E., Durivault, J., Dufies, M., Ambrosetti, D., Luciano, F., Gao, J., Cao, Y., Pagès, G., Giuliano, S. (2026) Connective tissue growth factor contributes to resistance to anti-angiogenic therapies in renal cancer. Theranostics. 16:448945074489-4507.
Abstract
Background Clear cell renal cell carcinoma (ccRCC) is predominantly treated with anti-angiogenic therapies (AATs), such as sunitinib and axitinib. While these therapies initially improve outcomes, resistance frequently emerges, limiting long-term efficacy. Understanding the molecular mechanisms underlying AAT resistance is essential to optimize treatment strategies.
Methods To identify factors involved in AAT resistance, we performed integrated transcriptomic and proteomic analyses on ccRCC cell lines subjected to either transient AAT treatment or with established acquired resistance. Functional validation was performed using in vitro assays (proliferation, migration, invasion) and in vivo zebrafish models. Plasma levels of candidate proteins were also measured in ccRCC patients and correlated with clinical outcomes.
Results Connective Tissue Growth Factor (CTGF) was consistently upregulated following treatment and in resistant cell lines. CTGF, a secreted protein regulated by Yes-associated protein (YAP) in the Hippo pathway, is known to promote angiogenesis, fibrosis, and tumor progression. Functionally, CTGF enhanced tumor cell aggressiveness in vitro and in vivo. Patient-derived samples also exhibited elevated CTGF levels in resistant tumors. Crucially, higher plasma CTGF levels were associated with shorter progression-free survival in ccRCC patients receiving AATs.
Conclusion CTGF is a key mediator of resistance to AATs in ccRCC, by promoting tumor progression and remodeling the tumor microenvironment. CTGF may thus serve as both a predictive biomarker and a therapeutic target. These findings support further investigation of CTGF inhibition as a strategy to overcome AAT resistance and improve treatment outcomes in ccRCC patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping