-Review-

Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features

Akiko Tonooka^1,2 and Ryuji Ohashi³

¹Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
²Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Komagome Hospital, Tokyo, Japan
³Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan

Among recent advances in cancer treatment, the emergence of novel drugs targeting specific molecules has considerably modulated therapeutic strategies. Despite the efficacy of these agents, renal complications that are distinct from those of conventional chemotherapeutic drugs have been reported. Targeted therapy drugs include monoclonal antibodies and small-molecule agents. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) and blocks tumor angiogenesis. This anti-angiogenic effect causes endothelial injury, resulting in "thrombotic microangiopathy-like lesions" confined to the glomerulus. Segmental hyalinosis of the glomerular tuft is also observed. Small molecular agents, including tyrosine kinase inhibitors (TKIs) such as pazopanib, can cause endothelial injury and podocytopathy by blocking VEGF receptors and their downstream signaling. Minimal change nephrotic syndrome and focal segmental glomerulosclerosis are associated with TKI-induced renal complications. Immune checkpoint inhibitors (ICIs) such as PD-1, CTLA-4, and PD-L1 modulate immune checkpoints and are a novel form of immunotherapy against cancer. Owing to their unique function, ICIs cause inflammatory side effects referred to as immune-related adverse events (irAEs). irAEs in the kidney include acute tubulointerstitial nephritis and tubulitis, occasionally accompanied by granuloma formation. Vasculitis, thrombotic microangiopathy, and glomerulonephritis have also been 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 clinicohistopathological aspects of renal complications associated with molecular targeted therapies and focus on anti-VEGF agents and immune checkpoint inhibitors from a pathological perspective.

J Nippon Med Sch 2022; 89: 128-138

Keywords
onconephrology, targeted therapy, anti-VEGF, immune checkpoint inhibitors, histopathology

Correspondence to
Ryuji Ohashi, MD, PhD, Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
r-ohashi@nms.ac.jp

Received, May 8, 2021
Accepted, September 15, 2021