Relationships between the Effect of Sunitinib and Immature Blood Vessels in Metastatic Renal Cell Cancer

Abstract

Introduction: This study was conducted to investigate the relationships between the effect of sunitinib and immature microvessels which are not covered by pericytes. Materials and Methods: This study involved 29 patients with clear-cell renal cell carcinoma (RCC) who took sunitinib after radical nephrectomy or biopsy due to metastatic RCC. Associations among clinicopathological factors, responses to sunitinib, and patient survival were reviewed. CD31 was used to stain endothelial cells, and anti-α-smooth muscle actin was used to stain pericytes. Immature vessels were defined as vessels that were positive only for CD31 staining. A high pericyte coverage was defined as a rate of pericyte coverage above 40%. Results: Partial responses, disease stabilization, and disease progression constituted 51.7, 10.4, and 37.9% of cases, respectively. Nine cases had a low pericyte coverage (31.0%). In the high-pericyte-coverage group, the number of metastatic sites was smaller (p = 0.003). The overall response rate to sunitinib was greater in the high-pericyte-coverage group than in the low-pericyte-coverage group (p = 0.027). The median overall survival and the median progression-free survival were not significantly different between the high- and low-pericyte-coverage groups. Conclusion: In the high-pericyte-coverage group, the overall response rates to sunitinib were higher, and the numbers of metastatic sites were smaller.

RET mutation and increased angiogenesis in medullary thyroid carcinomas

“…If this assumption is correct, one might reasonably expect this combination therapy to produce particularly obvious benefits in RETmut MTCs than in those without these mutations. Indirect support for this hypothesis has emerged from a recent study on metastatic clear-cell renal cell carcinomas, which showed that the subset of tumors whose vasculatures displayed high pericyte coverage tumors responded better than tumors without this feature to treatment with sunitinib, a multikinase inhibitor with strong effects on both PDGFRb and VEGFRs (Kim et al 2014). Additional preclinical evidence is needed, however, before this hypothesis can be adequately evaluated.…”

Combination therapy using molecular‐targeted drugs modulates tumor microenvironment and impairs tumor growth in renal cell carcinoma

“…Although a therapy targeting VEGF receptors on immature neovessels in tumors has attracted attention as a new approach for antiangiogenic therapy , its therapeutic effect is insufficient because of abnormal induction of pericytes in tumor tissue. In RCC, the overall response rate to sunitinib has been reported to be greater in the high‐pericyte‐coverage group than in the low‐pericyte‐coverage group . Additionally, increased extracellular matrices in solid tumors elevate interstitial pressure, in turn reducing the tissue distributions of antitumor drugs which suggests the importance of the role of the PDGF‐receptor signaling pathway in controlling the interstitial pressure in tumors .…”