Abstract
For a long time, cisplatin-based chemotherapy had been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC had been classified as cisplatin-ineligible who can only receive alternative chemotherapy with poor treatment response, and the vast majority of the cisplatin-eligible patients eventually progressed, even those with objective response with cisplatin-based chemotherapy initially. By understanding tumor immunology in UC, immune checkpoint inhibitors, targeting on programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) pathways, had been proven as first-line treatment for cisplatin-ineligible metastatic UC and as second-line treatment for patients with platinum-refractory metastatic UC by the U.S Food and Drug Administration (FDA). In 2020, JAVEIN bladder 100 further reported that PD-L1 inhibitors showed benefits on prolonged survival and progression-free survival as maintenance therapy. Besides targeting on immune checkpoint, manipulation of the tumor microenvironment by metabolic pathways intervention, including inhibition on tumor glycolysis, lactate accumulation and exogenous glutamine uptake, had been investigated in the past few years. In this comprehensive review, we start by introducing traditional chemotherapy of UC, and then we summarize current evidences supporting the use of immune checkpoint inhibitors and highlight ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting on metabolic pathways.
Highlights
Bladder cancer is the most common malignancy involving the urinary system and a common malignancy worldwide
Since the first efficacy immunotherapy for non-muscle invasive bladder cancer, bacillus Calmette-Guérin (BCG), was established by Morales and associates in 1976 [1], no immunotherapy has been approved and cisplatin-based chemotherapy has been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinomas (UCs) for a long time
We introduce traditional chemotherapy of UCs and summarize current evidences supporting the use of immune checkpoint inhibitors in advanced urinary system malignancy
Summary
Bladder cancer is the most common malignancy involving the urinary system and a common malignancy worldwide. Since the first efficacy immunotherapy for non-muscle invasive bladder cancer, bacillus Calmette-Guérin (BCG), was established by Morales and associates in 1976 [1], no immunotherapy has been approved and cisplatin-based chemotherapy has been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinomas (UCs) for a long time. With the better understanding of cancer immunology, immune checkpoint inhibitors and metabolic pathway intervention have been investigated to break this therapeutic stalemate in the past few years [2,3]. We introduce traditional chemotherapy of UCs and summarize current evidences supporting the use of immune checkpoint inhibitors in advanced urinary system malignancy. We review the new approaches of immune oncology via metabolic pathways
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