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Microbes & Immunity The feature of bladder cancer stem cells

of BC stood at 7.3 cases per 100,000 males, which was four median overall survival in certain patients with advanced
times higher than the incidence rate observed in females or high-grade BC (7.4 months in the chemotherapy group
(1.8/100,000). Smoking is the foremost risk factor for BC, compared to 10.3 months in the pembrolizumab group).
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with current smokers exhibiting a relative risk ratio of However, this approach is applicable to only 10 – 20%
2.94 for developing BC compared to those who have never of BC patients and is associated with high treatment
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smoked. Notably, prolonging the duration of smoking costs and prolonged treatment durations. 13-15 Due to
cessation can significantly decrease the incidence rate of the high recurrence rate of BC, patients with advanced-
BC. For instance, when the duration of smoking cessation stage BC often experience disease progression even after
persists for 10 years or more, the risk rate decreases from undergoing chemotherapy and immunotherapy. Oncolytic
4 to 2. In addition to smoking, occupational exposure, viruses, a form of novel immunotherapy, have presented
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urinary tract infections, bladder stones, and medications promising effects in high-risk and BCG-unresponsive
such as cyclophosphamide are major factors contributing NMIBC in clinical trials. Specifically, a phase III clinical
to the progression of BC. 3-6 trial conducted in 2023 (NCT04452591) observed a 75.7%
In BC, transitional cell carcinoma accounts for complete remission rate with no grade 3 or above adverse
90% of cases, while squamous cell carcinoma and events noted under oncolytic virus treatment.
adenocarcinoma, respectively, account for 2 – 3%. BC Targeted therapy has emerged as a promising avenue
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can be categorized based on the degree of infiltration into for treating BC patients. A phase III clinical trial conducted
muscle-invasive and non-muscle-invasive types. Non- by Thomas Powles and colleagues at the Barts Cancer
muscle invasive BC (NMIBC) constitutes 70% of all BC Centre, Queen Mary University of London, investigated
cases and is characterized by a favorable prognosis and the antibody-drug conjugate enfortumab vedotin. This
a high recurrence rate (31 – 78%). Conversely, muscle- compound exerts its effect by targeting Nectin-4, a protein
invasive BC (MIBC) constitutes 30% of all BC cases commonly overexpressed in BC. Patients receiving
and is characterized by a high rate of metastasis and treatment with enfortumab vedotin demonstrated a
poor prognosis. The most significant genetic variations prolonged median overall survival of 12.88 months
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contributing to BC involve cell cycle regulation signaling (compared to 8.97 months in the chemotherapy group).
pathways (TP53, PTEN, SMC1A, SMC1B, etc.), chromatin In addition, the median progression-free survival was
regulation (MLL2, ARID1A, BPTF, CHD6, etc.), kinase longer in the enfortumab vedotin group compared to the
signaling pathways (FGFR3, ERBB2, ERBB3, etc.), and the chemotherapy group (5.55 months versus 3.71 months).
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TERT gene. 8 Amplification and overexpression of FGFR were observed
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In clinical practice, primary diagnostic methods for BC in approximately 20% of advanced-stage BC patients.
include cystoscopy, urinary tract cytology examination, In phase II clinical trial of erdafitinib (a FGFR inhibitor)
imaging studies, and tumor marker testing. Cystoscopy, for the treatment of advanced BC patients with FGFR3
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regarded as the gold standard for BC examination, exhibits mutations and resistance to platinum-based drugs, it was
a diagnostic sensitivity exceeding 90%. However, being found that 80% of the patients exhibited a 42% objective
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an invasive procedure, it faces challenges such as patient response rate and disease control. While targeted
reluctance and the potential for inducing urethral bleeding. therapies have expanded the treatment options for BC
Urinary tract cytology examination demonstrates high patients, inevitable drug resistance eventually leads to the
specificity (95%) and addresses discomfort associated occurrence of refractory BC, leaving recurrent BC patients
with frequent cystoscopy. However, its sensitivity (13 with fewer treatment options. It is imperative to discover
– 75%) does not consistently achieve satisfactory levels more effective treatments to address this challenge.
of performance. Nonetheless, it remains an important Tumor stem cells (TSCs), as a subset of the tumor cells,
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supplementary method for BC assessment. At present, exhibit characteristics such as self-renewal, differentiation
urine markers such as nuclear matrix protein 22 (NMP22), potential, drug resistance, metastatic ability, and robust
fluorescence in situ hybridization, and bladder tumor tumorigenicity. Investigating the molecular phenotype of
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antigen are also utilized in detecting BC. 11 TSCs and implementing targeted therapies based on the
Surgical resection, radiotherapy, chemotherapy, and relevant research holds promise as an effective treatment
immunotherapy are the primary methods used in the strategy. TSCs play a crucial role in maintaining the stem
clinical treatment of BC. Recently, a substantial number cell pool within tumors and can differentiate into non-
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of immunotherapeutic agents have been incorporated stem cells. These tumor non-stem cells display rapid
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into clinical trials targeting advanced metastatic BC. proliferation capabilities but lack self-renewal abilities.
These trials have demonstrated a significant increase in TSCs often undergo adaptations to resemble stem cells

Volume 1 Issue 1 (2024) 26 doi: 10.36922/mi.2377