ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
sFRP2 Supersedes VEGF as an Age-related Driver of Angiogenesis in Melanoma, Affecting Response to Anti-VEGF Therapy in Older Patients.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Circulating galectin-1 delineates response to bevacizumab in melanoma patients and reprograms endothelial cell biology.Proceedings of the National Academy of Sciences of the United States of America · 2023Trial
- Single-cell immunoprofiling reveals a dysfunctional-like immune microenvironment and malignant phenotype in aging penile squamous cell carcinoma.Cell biology and toxicology · 2026Article
- Of Barriers and Loops-How Evolution Limits Most Cancer Risks to Older Ages.Cancer discovery · 2026Review
- Secreted frizzled-related protein 2 as a context-dependent extracellular signaling hub in development, tissue remodeling, and disease.Frontiers in cell and developmental biology · 2026Review
- Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications.Angiogenesis · 2025Review
- Secreted frizzled-related protein 2 monoclonal antibody-mediated IFN-ϒ reprograms tumor-associated macrophages to suppress triple negative breast cancer.Breast cancer research : BCR · 2025Article
- Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer.Nature reviews. Cancer · 2025Review
- Temporal vascular pattern remodeling mediated by the FHL2/sFRP2 signaling pathway in tenocytes affects tendon repair and regeneration.Experimental & molecular medicine · 2025Article
- High expression of eIF4A1 promotes angiogenesis through the NF‑κB/VEGFA pathway and predicts poor prognosis in gastric cancer.Oncology reports · 2025Article
- PDGFR-α shRNA-polyplex for uveal melanoma treatment via EMT mediated vasculogenic mimicry interfering.Journal of nanobiotechnology · 2024Article
- Exosomal miR-320d promotes angiogenesis and colorectal cancer metastasis via targeting GNAI1 to affect the JAK2/STAT3 signaling pathway.Cell death & disease · 2024Article
- Machine learning reveals CAT gene as a novel potential diagnostic and prognostic biomarker in non-small cell lung cancer.Discover oncology · 2024Article
- Article
- lnsights into Adjuvant Systemic Treatment Selection for Patients with Stage III Melanoma: Data from the Dutch Cancer Registry.Targeted oncology · 2024Article
- Determinants of resistance and response to melanoma therapy.Nature cancer · 2024Review
- Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development.International journal of molecular sciences · 2024Review
- Considerations and Approaches for Cancer Immunotherapy in the Aging Host.Cancer immunology research · 2023Review
- Histological characteristics of exercise-induced skeletal muscle remodelling.Journal of cellular and molecular medicine · 2023Article
- Challenges and opportunities for modeling aging and cancer.Cancer cell · 2023Article
- Secreted frizzled related-protein 2 is prognostic for human pancreatic cancer patient survival and is associated with fibrosis.Cancer biomarkers : section A of Disease markers · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeAngiogenesis is thought to be critical for tumor metastasis. However, inhibiting angiogenesis using antibodies such as bevacizumab (Avastin), has had little impact on melanoma patient survival. We have demonstrated that both angiogenesis and metastasis are increased in older individuals, and therefore sought to investigate whether there was an age-related difference in response to bevacizumab, and if so, what the underlying mechanism could be. EXPERIMENTAL
designWe analyzed data from the AVAST-M trial of 1,343 patients with melanoma treated with bevacizumab to determine whether there is an age-dependent response to bevacizumab. We also examined the age-dependent expression of VEGF and its cognate receptors in patients with melanoma, while using syngeneic melanoma animal models to target VEGF in young versus old mice. We also examined the age-related proangiogenic factor secreted frizzled-related protein 2 (sFRP2) and whether it could modulate response to anti-VEGF therapy.
resultsWe show that older patients respond poorly to bevacizumab, whereas younger patients show improvement in both disease-free survival and overall survival. We find that targeting VEGF does not ablate angiogenesis in an aged mouse model, while sFRP2 promotes angiogenesis
conclusionsVEGF is decreased during aging, thereby reducing response to bevacizumab. Despite the decrease in VEGF, angiogenesis is increased because of an increase in sFRP2 in the aged tumor microenvironment. These results stress the importance of considering age as a factor for designing targeted therapies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.