The evolving role of checkpoint inhibitors in the treatment of urothelial carcinoma

Abstract

The most prevalent pathological subtype of bladder and upper urinary tract malignancy is urothelial carcinoma (UC). Traditional therapies mainly include surgical resection, chemotherapy and radiotherapy. Checkpoint inhibitors, which are monoclonal antibodies developed to specifically target immune checkpoint molecules, have recently emerged as potential treatment options for UC patients, especially those targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). However, anti-PD-1/PD-L1 therapy does not work for a considerable number of UC patients. Current antitumour immunotherapy research hotspots include seeking biomarkers that might predict therapeutic effects and exploring novel immune checkpoint molecules crucial for the antitumour immune response. Hence, we will recapitulate the latest preclinical and clinical trials of 5 PD-1/PD-L1 inhibitors, 1 cytotoxic T-lymphocyte-associated protein 4 inhibitor and combination therapies for UC treatment, including combined immunotherapy and immunotherapy with chemotherapy or radiotherapy. We will also summarize other potential immune checkpoint molecules found in ongoing UC studies. Moreover, we will highlight the role of biomarkers linked with the oncological efficacy of anti-PD-1/PD-L1 immunotherapy and address the mechanisms of immunotherapy drug resistance in UC, with the hope of providing more systematic guidance for its application and development.