Current trends of anti-cancer molecular targeted therapies: a narrative review focusing on renal complications and their histological features

抄録

Among the recent advancements in cancer treatment, the emergence of novel drugs targeting a specific molecule has considerably modulated the therapeutic strategies. Despite the efficacy, the associated renal complications distinct from conventional chemotherapeutic drugs have been reported. Targeted therapy drugs include monoclonal antibodies and small molecule agents. Bevacizumab is one of the monoclonal antibodies that targets vascular endothelial growth factor (VEGF) and blocks tumor angiogenesis. This anti-angiogenic effect causes endothelial injury, resulting in "thrombotic microangiopathy-like lesion" confined to the glomerulus. Segmental hyalinosis of the glomerular tuft is also observed. The small molecular agents, including tyrosine kinase inhibitors (TKIs), such as pazopanib, can cause endothelial injury and podocytopathy through blocking VEGF receptors and their downstream signaling. Minimal change nephrotic syndrome and focal segmental glomerulosclerosis are associated with TKIs-induced renal complications. Immune checkpoint inhibitors (ICIs), such as PD-1, CTLA-4 and PD-L1, are a novel form of immunotherapy against cancer, which modulates immune checkpoints. Owing to its unique function, ICIs cause inflammatory side effects referred to as immune-related adverse events (irAEs). irAEs in the kidney commonly include acute tubulointerstitial nephritis and tubulitis, occasionally accompanied by granuloma formation. The occurrence of vasculitis, thrombotic microangiopathy, and glomerulonephritis is also reported. Renal toxicity associated with other molecular drugs such as protease inhibitors and mammalian target of rapamycin inhibitors has also been documented. In this article, we review the clinico-histopathological aspects of renal complications associated with molecular targeted therapies, focusing on anti-VEGF agents and immune checkpoint inhibitors from the pathologists' viewpoint.