Angiogenesis and angiogenic inhibitors in renal cell carcinoma

Abstract

In most patients with renal cell carcinoma (RCC) of clear cell subtype, there is inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene, which leads to a proangiogenic state with overexpression of vascular endothelial growth factor (VEGF). This molecular level knowledge has led to the development of multiple antiangiogenic therapies directed against the VEGF protein or the VEGF receptor. These therapies have significant clinical activity in metastatic RCC. Therefore, a therapeutic strategy based on targeting VEGF in RCC has a sound molecular basis and therapy with VEGF-targeting agents has significant clinical activity. To further improve efficacy, future research should focus on better identification of patients who will most benefit from such therapy. We reviewed the published literature regarding angiogenesis, the VHL gene, VEGF biology, and antiangiogenic therapies in metastatic RCC. This article reviews the role of angiogenesis in RCC and summarizes data regarding antiangiogenic therapy in metastatic RCC.

Impact of Tumor Vascularity on Responsiveness to Antiangiogenesis in a Prostate Cancer Stem Cell-Derived Tumor Model

“…Tumor vascularity varies widely in human cancers, ranging from highly vascularized renal carcinomas (15, 16) to poorly vascularized prostate cancer (17), reflecting, in part, the balance between pro- and anti-angiogenic factors within the tumor microenvironment (4, 18). Vascularity is an independent prognostic factor for many human tumors, with high vascular density often associated with poor prognosis following surgery or conventional chemo/radiotherapy (19, 20).…”

Pazopanib-induced trismus in a young male with metastatic renal cell carcinoma: a case report and literature review

“…Renal cancer has been a proof-of-concept model for targeting angiogenesis [ 2 ]. Hereditary and most sporadic renal cell carcinoma originate from the loss-of-function mutation of the Von-Hippel Lindau (VHL) gene, which leads to hyperactivation of the hypoxia-inducible factors (HIF-1α and HIF-2α) normally expressed under hypoxia, and thus an overexpression of VEGF and other proangiogenic factors [ 3 ].…”

Local recurrence of renal cell carcinoma that simulated multiple renal arteriovenous fistulas after laparoscopic partial nephrectomy: Report of a rare case

“…RCC is a hypervascular adenocarcinoma that requires angiogenesis‐inducing factors for its characteristic growth pattern . High vascular density and small arteriovenous shunts that provide a rich blood supply facilitate aggressive behavior and vascular permeability .…”

“…Editorial Comment to Local recurrence of renal cell carcinoma that simulated multiple renal arteriovenous fistulas after laparoscopic partial nephrectomy: Report of a rare case Partial nephrectomy (PN) is the gold standard treatment for clinically localized cT1 renal cell carcinoma (RCC), regardless of the surgical approach. 1 Avoiding positive surgical margins, 2 reducing the rate of perioperative complications and keeping the warm ischemia time as low as possible are the mainstay of any PN. 1 In this context, among minimallyinvasive approaches, laparoscopic PN is still a technically demanding procedure, 3 with a higher morbidity profile and poorer intraoperative outcomes when compared with robotassisted PN.…”

“…1 Avoiding positive surgical margins, 2 reducing the rate of perioperative complications and keeping the warm ischemia time as low as possible are the mainstay of any PN. 1 In this context, among minimallyinvasive approaches, laparoscopic PN is still a technically demanding procedure, 3 with a higher morbidity profile and poorer intraoperative outcomes when compared with robotassisted PN. 4 In the present case report, Aydin et al presented, for the first time, a case of locally recurrent RCC mimicking multiple arteriovenous fistulas (AVF) in a male patient treated with laparoscopic right PN for cT1 renal mass.…”