Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review

Abstract

Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.

Tumor-Associated Mast Cells in Urothelial Bladder Cancer: Optimizing Immuno-Oncology

“…Urothelial bladder cancer (UBC) is a common disease with high morbidity and mortality rates, accounting for around 2.1% of all deaths due to cancer per year [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. As the high rate of recurrence and the need for long-term surveillance greatly increased the economic burden of UBC patients, exploring optimized and personalized therapeutic modalities against UBCs is a rapidly evolving and expanding field in adjuvant and definitive settings [ 4 , 8 , 9 ]. Tumoral depth of invasion and detrusor invasiveness are the most significant variable for progression, recurrence, and survival in UBC [ 6 ].…”

“…At presentation, about 70% of patients with UBC present with disease confined to the mucosa (stage Ta or carcinoma in situ) or submucosa (stage T1) (non–muscle-invasive bladder cancer, NMIBC), which has a good prognosis [ 1 , 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. NMIBC includes a diverse spectrum of diseases with a wide range of progression and recurrence rates that depend on several clinical and pathologic factors; thus, the key to improving the prognosis of NMIBC is to reduce the risk of recurrence and progression [ 3 , 4 , 7 , 9 , 11 ]. Standard treatment of NMIBC involves transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy and/or bacillus Calmette-Guerin (BCG), in a risk-adapted manner [ 3 , 4 , 7 , 9 , 11 , 12 ].…”

“…NMIBC includes a diverse spectrum of diseases with a wide range of progression and recurrence rates that depend on several clinical and pathologic factors; thus, the key to improving the prognosis of NMIBC is to reduce the risk of recurrence and progression [ 3 , 4 , 7 , 9 , 11 ]. Standard treatment of NMIBC involves transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy and/or bacillus Calmette-Guerin (BCG), in a risk-adapted manner [ 3 , 4 , 7 , 9 , 11 , 12 ]. Especially, intravesical BCG is typically reserved for high-risk patients in the first-line setting, or as an option for intermediate-risk patients [ 3 , 4 , 7 , 8 , 9 , 11 , 12 ].…”

“…Standard treatment of NMIBC involves transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy and/or bacillus Calmette-Guerin (BCG), in a risk-adapted manner [ 3 , 4 , 7 , 9 , 11 , 12 ]. Especially, intravesical BCG is typically reserved for high-risk patients in the first-line setting, or as an option for intermediate-risk patients [ 3 , 4 , 7 , 8 , 9 , 11 , 12 ]. Different options exist upon failure of first-line treatment, i.e., following failure of intravesical chemotherapy or BCG, and are largely dependent on the response to prior therapy [ 4 , 9 , 11 , 12 ].…”

“…Especially, intravesical BCG is typically reserved for high-risk patients in the first-line setting, or as an option for intermediate-risk patients [ 3 , 4 , 7 , 8 , 9 , 11 , 12 ]. Different options exist upon failure of first-line treatment, i.e., following failure of intravesical chemotherapy or BCG, and are largely dependent on the response to prior therapy [ 4 , 9 , 11 , 12 ]. Following BCG failure in high-risk NMIBC, the standard of care is radical cystectomy, which is associated with considerable morbidity and mortality, particularly in older and frailer patients [ 3 , 4 , 7 , 12 ].…”