Urothelial bladder cancer immunotherapy strategies

Abstract

Bladder cancer is a highly heterogeneous malignant disease and is associated with various molecular characteristics and distinctive clinical outcomes. Bladder cancer is one of the most important health problems due to its incidence, increased risk of recurrence and failure in therapy. For locally advanced and metastatic urothelial bladder cancer patients, the current standard treatment involves platinum-based combination chemotherapy. Nevertheless, up to half of the patients are refractory or ineligible for platinum-based chemotherapy and also toxicity is significant. Recent advances in molecular and genetic studies have revealed new insights into the predictive and prognostic biomarkers and potential therapeutic targets of bladder cancer. Immunotherapy is a novel promising targeted therapy for cancer treatment. Several approaches contributing to tumor recognition and cell death by the immune system have been adopted in oncology, such as immune checkpoint inhibitors, monoclonal antibodies, tumor vaccines, small molecules, and chimeric antigen receptor T-cells (CAR-T cells). The most frequently used form of immunotherapies are immune checkpoint inhibitors. Especially, immunecheckpoint blockade therapy provides rapid and durable antitumor responses in malignancies including bladder cancer. Immune-checkpoint inhibitors are key regulators of the adaptive immune system and promote anti-tumor activity by targeting the pathways which cancer cells exploit to escape from the host immune system. The approved cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death 1 (PD1) and programmed death ligand 1 (PDL1) checkpoint inhibitors have shown improved clinical efficacy in patients with metastatic platinum-refractory urothelial bladder cancer. However, most patients are not responsive to such treatment strategies. Further preclinical and clinical research is ongoing to improve new combinational immunotherapy strategies for patients with bladder cancer. © 2020 by Nova Science Publishers, Inc. All rights reserved.