A recent study published in Clinical Cancer Research and conducted in France has identified potential biological markers that are related to the formation of new blood vessels (angiogenesis) and regulated by the levels of oxygen reaching the tissues (hypoxia). These biomarkers have been found to be strong predictors of response, progression-free survival (PFS), and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who were being treated with sunitinib before they have their kidney removed by surgery (nephrectomy).
The phase 2 PREINSUT study involved 32 patients scheduled for nephrectomy. The researchers assessed their response to treatment with two cycles of sunitinib to see if the presence of certain biomarkers circulating in their blood could indicate whether sunitinib (a tyrosine kinase inhibitor, TKI) was working.
The researchers identified the following biomarkers, which were significantly associated with response to treatment with sunitinib:
- Endothelial progenitor cells, which are thought to affect tumour size
- Platelet-derived growth factor (PDGF)-BB, thought to be linked to tumour size
- High levels of vascular endothelial growth factor (VEGF)-A, linked to progression-free survival
- High levels of stromal cell-derived factor-1 (SDF-1), linked to overall survival and tumour size
- Levels of soluble VEGF receptor 1 (sVEGFR1), linked to overall survival
- Low levels of soluble VEGF receptor 2 (sVEGFR2), linked to progression-free survival.
Other targeted therapies used in the treatment of metastatic RCC that also target the VEGF pathway include sorafenib, bevacizumab, pazopanib, axitinib, everolimus and temsirolimus.
The investigators concluded that tumours with a poor blood supply appeared to be associated with worse outcomes, and “angiogenesis-related parameters have a promising place in therapy guidance and should be evaluated on a larger scale.”