Predictive biomarkers for drug response in bladder cancer

Abstract

Bladder cancer is a heterogeneous disease. Interpatient heterogeneity in response to a drug limits treatment options and impairs improvement of patient survival. For example, approximately half of patients do not respond to cisplatin-based combination chemotherapy, although it is the standard of care for muscle-invasive and metastatic bladder cancer. The development of robust predictive biomarkers is expected to improve outcomes by enabling clinicians to use chemotherapy only in the patients who will benefit from it. Recent advances in the molecular characterization of bladder cancer showed that the basal subtype of bladder cancer and tumors with inactivating mutations in DNA damage repair genes were associated with greater benefit from cisplatin-based chemotherapy. The present review summarizes current efforts to develop predictive biomarkers for drug response in bladder cancer, focusing on those that predict the response to cisplatin-based chemotherapy for advanced bladder cancer. We also review the current situation with regard to the identification of predictive biomarkers for response to intravesical therapy, immune checkpoint inhibitors and molecularly-targeted drugs. We also discuss the future applications of new technologies, including liquid biopsies and patient-derived organoids that will also serve as resources for the identification of biomarkers in bladder cancer.

Keywords: cisplatin; drug response; neoadjuvant chemotherapy; predictive biomarker; urothelial cancer.