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Circulating cytokines and monocyte subpopulations as biomarkers of outcome and biological activity in sunitinib-treated patients with advanced neuroendocrine tumours
- Source :
- British Journal of Cancer
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Background: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. Methods: Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. Results: Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. Conclusions: Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.
- Subjects :
- carcinoid
Cancer Research
Disease free survival
Indoles
Treatment outcome
Antineoplastic Agents
Carcinoid Tumor
pro-tumorigenic myeloid cells
Neuroendocrine tumors
Biology
urologic and male genital diseases
Disease-Free Survival
Monocytes
Leukocyte Count
Biomarkers, Tumor
Sunitinib
medicine
Humans
Pyrroles
Monocyte
cellular responses to anticancer drugs
circulating biomarkers
Biological activity
medicine.disease
pancreatic neuroendocrine tumours
female genital diseases and pregnancy complications
Neuroendocrine Tumors
Circulating biomarkers
Treatment Outcome
medicine.anatomical_structure
Oncology
Immunology
Cytokines
Female
Translational Therapeutics
Tumor immunology
medicine.drug
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....ab861164abb78946d4c78ae1a0320881