Bladder Cancer

Expression of Trop-2 and ephrin B2 may demonstrate therapeutic possibilities for patients with SH/DD, who usually have limited treatment options, particularly in small cell carcinoma, in which few targets have been identified. Clinical trials to investigate the efficacy of these novel treatments are warranted.

Functional analyses have revealed that IL4I1 may promotes tumor progression in recurrent tumors by activating the aryl hydrocarbon receptor (AHR) and recruiting regulatory T cells to suppress adaptive immunity. Taken together, our study provides a comprehensive understanding of primary and recurrent multifocal bladder tumors, offering valuable resources for analyzing the multifocality and recurrence of bladder cancer.

The KO of OXCT1 restored OVOL1 transcriptional repressive activity by its nuclear translocation. Orthotopic mouse models of BCa supported OXCT1 as a mediator of gemcitabine sensitivity through ketone metabolism and regulating cancer stem cell differentiation.

P2, N=27, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2024 --> Nov 2025

Additionally, CXCL1 secretion from BC cells was found to contribute to the M2-like polarization of macrophages and to enhance BC cell migration and invasion through autocrine and indirect effects. In summary, CCL20 and CXCL1 play crucial roles in the interaction between BC cells and TAMs.

Together, these preclinical data support the potential utility of VB-85247 for treating BCG-unresponsive NMIBC patients and for enhancing the clinical benefit of potential of anti-PD1 in bladder cancer. Based on these data, VB-85247 is being advanced into clinical development.

Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers.

It is rare for NAs of the bladder to develop to mesonephric adenocarcinomas of the bladder, and pathological immunohistochemistry staining is used to make the definitive diagnosis. The high proliferation activity of carcinoembryonic antigen (CEA) (+), P53(+), and Ki-67 are important molecular markers for identifying the malignant transformation of NA, as well as the elevation in the Ki-67 proliferation index.

We propose that TWIST1 holds great promise as a diagnostic and therapeutic target for BLCA, with the potential to influence tumor progression and patient prognosis through the regulation of immune cell infiltration. We hope these findings contribute valuable insights to the field of BLCA research.

Both cell types showed disruptions in the cell cycle but at different points in the cycle. These results show that MK2 controls irradiation-induced apoptosis in bladder cancer cells.

ARGs played an important role in the progression, immune infiltration, and prognosis of BLCA. The ARGs model has high accuracy in predicting the prognosis of BLCA patients and provides more effective medication guidelines.

ALK + ALCL involving the bladder is very rare, and early diagnosis is challenging. By reviewing the diagnostic and treatment process of this patient, and in conjunction with a review of modern literature on the disease's incidence characteristics, treatment protocols, and prognosis, this aims to provide a reference for clinicians in diagnosing and treating this condition, thereby reducing delays.

Fifty days post-admission, Mycobacterium bovis BCG was identified in the initial sputum cultures. Concomitant interstitial pneumonia and BCG infection should be considered in patients with abnormal chest imaging following intravesical BCG therapy.

The results demonstrated that Ir-Mito2 exhibited excellent antitumor efficacy with superior biosafety in vivo. This work on light-activated and mitochondrial-targeted PS provides an innovative therapeutic platform for BC.

Finally, we show seemingly for the first time that cinobufotalin promotes SIAH1/2-mediated proteasomal degradation of PPARγ in luminal BC cells. Together, these findings compellingly support the idea that cinobufotalin could be developed as a promising therapeutic agent for treating luminal-type NMIBC.

Our newly established prognostic signature, which involved eight LMGs, can give prognostic distinction for BLCA and may eventually lead to novel targets for treatment.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Sep 2025 | Trial primary completion date: Oct 2024 --> Sep 2025

P=N/A, N=167, Completed, Taproot Health | Recruiting --> Completed | N=100000 --> 167 | Trial completion date: Oct 2031 --> Oct 2024 | Trial primary completion date: Oct 2029 --> Oct 2024

Key regulators, including PERK, IRE1α, and ATF6, are discussed for their roles in upregulating CHOP levels and triggering apoptosis. In conclusion, a deeper understanding of ER stress in urological cancers not only clarifies the complex interactions between cellular stress and cancer progression but also provides new opportunities for innovative therapeutic strategies.

The findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting it as a promising target for macrophage-focused drug development.

P2, N=20, Not yet recruiting, Leslie Ballas | Initiation date: Jul 2024 --> Feb 2025

We also investigate how the IRF2-CXCL10 pathway induces T cell exhaustion and leads to immune escape. This research provides new insights into the immunotherapy of bladder cancer, highlighting potential molecular targets for more effective treatment strategies.

P2, N=60, Recruiting, John Sfakianos | Not yet recruiting --> Recruiting

P=N/A, N=190, Completed, Institut de Cancérologie de Lorraine | Recruiting --> Completed

According to the results of rescue experiments, HSPE1 regulated GPX4 to affect cell lipid peroxidation levels and GSH accumulation. HSPE1 plays a crucial role in regulating GPX4 to prevent BLCA cells from undergoing ferroptosis, with this control mechanism dependent on GSH.

Notably, high-risk patients demonstrated higher sensitivity to Sorafenib, Oxaliplatin and MK-2206, underscoring the promise of these lncRNAs as precise therapeutic targets in bladder cancer. By revealing the predictive importance of disulfidptosis-associated lncRNAs in bladder cancer, our research offers new perspectives and pinpoints potential therapeutic targets in clinical environments.

Today, novel agents called antibody drug conjugates (ADCs), including enfortumab vedotin (EV) and sacituzumab govitecan (SG), have been approved for la/mUC offering patients treatment options following or instead of traditional chemotherapy...In 2023, EV in combination with pembrolizumab almost doubled progression-free and overall survival versus platinum-based chemotherapy, which led to accelerated FDA approval as first-line treatment for all patients with la/mUC...Finally, a recent cancer agnostic accelerated approval for trastuzumab deruxtecan (T-DXd) in HER2-positive (IHC3+) solid tumors provides another active ADC option for biomarker-selected patients with treatment refractory la/mUC. Several new ADCs are being investigated in urothelial cancer (UC) clinical trials. This review summarizes the clinical studies and real-world data regarding the use of ADCs in UC.

Our results confirm the heterogeneity of CAF in both bladder and prostate tumors and indicate that FAP is one of CAF subpopulation marker.

Furthermore, M. brumae inhibited anchorage-independent growth across all BC lines, while M. bovis BCG had a more selective effect, primarily inhibiting growth in high-grade cells. In conclusion, both mycobacteria reduce migration, invasion, and anchorage-independent growth of BC cells, with their effectiveness varying by species and tumor differentiation grade.

This study links immune-inflammatory markers, HRV parameters, and psychosocial factors in BC, suggesting that immune and autonomic variations may relate to unfavourable outcomes. Incorporating these assessments could help tailor more personalised treatment strategies for BC patients.

Two enzymes involved in the heme synthesis pathway, coproporphyrinogen oxidase and ferrochelatase, exhibit a circadian rhythm. The fluorescence intensity started gradually increasing at 12 p.m., and the highest level was observed in patients who underwent surgery between 3 and 5 p.m. Our findings suggest that it may be possible to optimize the timing of the photodynamic diagnosis in photodynamic diagnosis-assisted transurethral resection of bladder cancer based on the circadian rhythm to improve tumor detection and treatment outcomes.

The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies.

Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.

In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.

Nude mice implanted subcutaneously with CDDP-resistant T24 cells were injected intraperitoneally with CDDP (2 mg/kg) every 3 days for 35 days and the results demonstrated that SRD5A3 knockdown and IGF2BP3 knockdown effectively inhibited the tumor growth in subcutaneous implantation model. Collectively, the study unveils that IGF2BP3-mediated SRD5A3 m6A modification facilitates bladder cancer progression and induces CDDP resistance, providing rational therapeutic targets for bladder cancer patients.

The combination of TURBT with pirarubicin and BCG intravesical instillation significantly lowers the recurrence rate in HRNMIBC patients and enhances both quality of life and immune function recovery. Independent factors affecting HRNMIBC recurrence include tumor number, stage, grade, and primary tumor status.

In conclusion, while bladder cancer biomarkers have shown great promise, more research is needed to standardize the testing procedures and validate these biomarkers in a clinical setting. This will pave the way for more accurate and efficient diagnosis and monitoring of bladder cancer, ultimately improving patient outcomes.

RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.

P=N/A, N=60, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P=N/A, N=30, Recruiting, University of Virginia | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Oct 2025

Clinically, BCa patients with increased mitochondrial TACO1 expression respond poorly to cisplatin treatment. This study elucidates the mechanisms by which TACO1 promotes BCa stemness and cisplatin resistance, providing a potential target for mitigating cisplatin resistance for BCa and a biomarker for predicting cisplatin response.

Analysis of the underlying mechanisms revealed that USP20 directly interacted with the YAP1 protein and promoted its stability through inhibition of K48-linked poly-ubiquitination. Our findings revealed that USP20 serves as a deubiquitinase and regulates the Hippo-YAP1 pathway in BC.