Skip to Main content Skip to Navigation
Journal articles

Clinical and kinomic analysis identifies peripheral blood mononuclear cells as a potential pharmacodynamic biomarker in metastatic renal cell carcinoma patients treated with sunitinib

Abstract : Background: Sunitinib is a protein tyrosine kinase (PTK) inhibitor that has immune-modulating properties. In this context, peripheral blood mononuclear cells (PBMC), mainly constituted by lymphocytes, could be a perfect surrogate tissue for identifying and assaying pharmacodynamic biomarkers of sunitinib. In this study, we investigated the changes in lymphocytes count as pharmacodynamic biomarker in metastatic renal cell carcinoma (mRCC) patients under sunitinib therapy. Thereafter, we studied the ex vivo effect of sunitinib and SU12262 (active metabolite) on PBMC from naïve mRCC patients using a high throughput kinomic profiling method. Methods: The prognostic value of total lymphocytes count between Day 0 and Day 21 (expressed as a ratio D21/D0) was retrospectively investigated in 88 mRCC patients under sunitinib therapy. PTK PamChip ® microarrays were used to explore prospectively the ex vivo effect of sunitinib and SU12662 on PTK activity in PBMC from 21 naïve mRCC patients. Results: In this retrospective study, D21/D0 lymphocytes ratio (Hazard Ratio, 1.83; CI95%, 1.24-2.71; p=0.0023) was independently associated with PFS. Interestingly, kinomic analysis showed that D21/D0 lymphocytes ratio and Heng prognostic model was statistically associated with the ex vivo sunitinib and SU12662 effect in PBMC. Conclusion: The present study highlights that D21/D0 total lymphocytes ratio could be a promising pharmacodynamic biomarker in mRCC patients treated with sunitinib. Additionally, it paves the way to investigate the kinomic profile in PBMC as a prognostic factor in a larger cohort of mRCC patients under sunitinib therapy.
Document type :
Journal articles
Complete list of metadatas

Cited literature [33 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01376706
Contributor : Mireille Bos <>
Submitted on : Wednesday, October 5, 2016 - 2:50:27 PM
Last modification on : Tuesday, July 21, 2020 - 3:59:19 AM
Long-term archiving on: : Friday, January 6, 2017 - 1:32:27 PM

File

11686-176325-2-PB.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Gaёlle Noé, Audrey Bellesoeur, Audrey Thomas-Schoemann, Savithri Rangarajan, Faris Naji, et al.. Clinical and kinomic analysis identifies peripheral blood mononuclear cells as a potential pharmacodynamic biomarker in metastatic renal cell carcinoma patients treated with sunitinib. Oncotarget, Impact journals, 2016, Epub ahead of print. ⟨10.18632/oncotarget.11686⟩. ⟨inserm-01376706⟩

Share

Metrics

Record views

445

Files downloads

1091