Approximatively 80% of kidney cancers globally are clear cell kidney cancers (ccRCCs), with 80% of these malignancies featuring an inactivating mutation of the Von Hippel-Lindau gene. This genetic alteration leads to the stabilization of hypoxia inducible factors 1 and 2 alpha (HIF 1 and 2α), resulting in the over-expression of target genes such as vascular endothelial growth factor (VEGF), which is crucial for angiogenesis. As a result, ccRCCs are highly vascularized and serve as models for anti-angiogenic treatments (AAT). Current AAT therapies comprise antibodies targeting VEGFs, tyrosine kinase inhibitors (TKi) (Sunitinib) that target neo-angiogenesis receptors, and competitive inhibitor receptors (Aflibercept) that trap VEGFA and PlGF. The over-expression of VEGF and related members such as VEGFC significantly influences angiogenesis, lymph-angiogenesis, and immune tolerance. This has resulted in the approval of various immune checkpoint inhibitors (known as anti-PD-1, anti-PD-L1, and anti-CTLA-4) as viable treatment options for kidney cancer. Despite these advances, ccRCC remains challenging to treat adequately. Thus, future research is imperative to better understand the biology and pathophysiology of RCC, the tumor microenvironment, and mechanisms of resistance, with the aim of developing new therapies.
Cancer diagnosis & prognosis. 2024 Sep 01*** epublish ***
Stefania Chipuc, Haineala Bogdan, Dragos Serban, Dumitru Cristinel Badiu, Anca Zgura, Rodica Anghel
Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania., Department of Urology, "Fundeni" Clinical Institute, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania., General Surgery Department, Emergency University Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania., General Surgery Department, "BagdasarArseni" Clinical Emergency Hospital, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.