Bladder Cancer

This single-cell analysis builds upon our understanding of the impact of Ad-IFNα on tumor cells and other compartments of the microenvironment. These data will help identify mechanisms to improve patient selection and therapeutic efficacy of Nadofaragene firadenovec.

The fact that hsa-miR-659-3p downregulates RON expression indicates its critical role in attenuating RON-mediated tumorigenic effect on bladder cancer cells. These findings highlight the importance of RON targeting as a therapeutic means for potential bladder cancer therapy.

Moreover, we also found that targeting NOTCH3 inhibited BLCA growth and metastasis by suppressing the SPP1-PI3K/AKT axis. Our study highlights the critical role of NOTCH3-SPP1-PI3K/AKT axis in the malignant progression of BLCA, suggesting that NOTCH3 may be a potential therapeutic target for BLCA.

P3, N=792, Active, not recruiting, Institut Bergonié | Unknown status --> Active, not recruiting | N=1500 --> 792 | Trial completion date: Feb 2021 --> Mar 2026 | Trial primary completion date: Feb 2019 --> Dec 2023

P=N/A, N=100, Not yet recruiting, Ziekenhuis Oost-Limburg

Additionally, low CLDN18.2 expression was linked to favorable prognosis. Our study reveals the potential value of CLDN18.2 for tumor prognosis and targeted therapy in various cancers, especially upper gastrointestinal tract cancers.

Furthermore, when combined with PD-1 blockade, engineered EcN amplified the antitumor antibody response and promoted long-term survival and protective immunity upon tumor rechallenge. Thus, we demonstrate that synthetically engineered CXCL13-expressing EcN can enhance the efficacy of PD-1 checkpoint blockade immunotherapy by amplifying tumor-specific humoral immunity.

In conclusion, there is good evidence of certain associations between genomic factors and relapse to SUD. However, further research is needed to ascertain causality effects of these factors and develop novel interventions for effective treatment and relapse prevention.

Our research provides insights into the significance of FOXK2 in cancer and indicates its potential as both a prognostic indicator and target for treatment. The ribosome-associated pathways involving FOXK2 and FBXO32 could be pivotal in the advancement of tumors, offering possible avenues for targeted and individualized immunotherapy approaches. Additional research is required to completely understand the mechanisms that are responsible for the participation of FOXK2 and its subsequent gene FBXO32 in cancer, as well as to explore the possible advantages of focusing on FOXK2 for cancer treatment.

Additionally, the report explores various aspects of having synchronous colorectal cancers. More studies are needed to clarify the clinicopathologic and molecular landscape of these rare tumors and identify the best management and treatment strategies for these patients.

Our study revealed the crucial role of the KLF16/MYC regulatory axis in modulating tumor growth and chemotherapy sensitivity in BLCA, suggesting that combining bromodomain inhibitors, such as OTX015 or ABBV-744, with DDP or gemcitabine could be a promising therapeutic intervention for BLCA patients.

This study reveals that susceptibility and bladder cancer aggressiveness are associated with polymorphisms at codon 751 and Asp/Asn at codon 312 of the ERCC2 gene.

Compared with the low-risk group, patients in the high-risk group demonstrated increased sensitivity to cisplatin, docetaxel, and paclitaxel. Furthermore, IGF2BP2, a potential target gene of MAFG-DT, was found to be overexpressed in tumor tissues and correlated with overall survival (OS). Our study demonstrated that the predictive signature based on eight redox-related lncRNAs can independently and accurately predict the prognosis of BCa patients.

KRT17 was not associated with tumor site, grade, or stage. In summary, K17 is a sensitive and specific marker of neoplastic upper tract urothelium, and its potential use in routine diagnostics should be explored in larger studies.

P3, N=1397, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder cancer immunotherapy.

Furthermore, SPARCL1 expression was positively related to TMB, immune activation processes, TIDE scores, immune checkpoint expression, and chemotherapeutic sensitivity in BCa. Our study highlights the potential involvement of SPARCL1 in macrophage recruitment and polarization and suggests its utility as a biomarker for prognosis in BCa.

Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN1254-1262 specific Opt TCR-T cells are promising candidates for CDDP combination therapy.

This suggests B7-H3's potential as a predictive biomarker for chemotherapy response. Further research is needed to explore the role of B7-H3 on platinum-based chemotherapy response in urothelial cancer.

A joint analysis of p63 and GATA3 did not suggest that GATA3 could provide additional prognostic information. The independent prognostic role of reduced p63 expression in advanced urothelial carcinomas suggests that p63 could be a useful biomarker to distinguish pT2-4 urothelial carcinomas.

Several studies have demonstrated that YAP1 is overexpressed in bladder cancer and is involved in adverse outcomes such as bladder cancer occurrence, progression, resistance to cisplatin and the recurrence of tumours...In addition, this study further explored the potential of YAP1 in the diagnosis and treatment of bladder cancer. This study aimed to explore the potential mechanism of YAP1 in the treatment of bladder cancer.

Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC)...Patients with high levels of NETs predicted poor response to neoadjuvant chemotherapy. This study was the first to reveal the correlation between the level of NETs in MIBC and the efficacy of chemotherapy, which may provide a theoretical basis regarding NETs inhibitors.

In conclusion, our studies highlight the critical role of LRRC45 in enhancing the stability of NRF2, thereby promoting the tumorigenic potential of bladder cancer. These insights suggest that targeting LRRC45 could serve as a promising molecular target for developing novel therapeutic interventions for bladder cancer.

More importantly, bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48% and sensitivity of 92.22% in 195 clinical specimens of bladder cancer patients. Taken together, this novel synergetic targeting (CD206 × CXCR4) strategy provides an attractive method for earlier detection of bladder cancer and metastasis, which might be further extended to the imaging-guided surgery of clinical invisible tumors.

Among these therapies, erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor for specific FGFR2 and FGFR3 alterations, is the only targeted therapy approved till now...Ongoing investigations exist on its use in non-muscle-invasive BC and in combination with drugs such as enfortumab vedotin in mUC...This review emphasizes the importance of FGFR inhibition in UC and the optimization of its use in clinical practice. Moreover, it underscores the ongoing efforts to evaluate combination strategies and early treatment testing to enhance the effectiveness of targeted therapies for UC.

The phenotypic analysis of these cultures by multi-parametric flow cytometry is explained. Functional assays, including lymphocyte degranulation, cytokine production and radioactive isotope-free specific lysis experiments are also described.

Our results suggested that high expression of USP1 promotes bladder cancer progression by stabilizing c-MYC; hence, USP1 may serve as a novel therapeutic target for treating bladder cancer.

It was found that HT inhibited the proliferation of BC cells by downregulating the phosphorylation of protein kinase B. Moreover, HT effectively enhanced the sensitivity of BC cells to the chemotherapy drug cisplatin (DDP) and reduced the chemoresistance of DDP‑resistant cells by downregulating the expression of cadherin‑11...In summary, the antineoplastic effects of HT were mediated through three main mechanisms: Enhancement of the chemosensitivity of BC cells and mitigation of DDP‑induced chemoresistance, suppression of the invasive potential of BC cells and reinforcement of the anticancer response of NK cells. Thus, HT appears to be a promising adjunctive therapy for human BC.

Since genetic alterations of the chromatin pathway genes are important in both UTUC and UCB, they could serve as potential biomarkers for predicting disease progression and therapeutic targets. Differences in mutation frequencies of DDR pathway, TMB, CNV, and TCR might be the contributing factors for the distinct responses to immune checkpoint inhibitor (ICI) between UTUC and UCB.

Furthermore, as in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), and kidney renal papillary cell carcinoma (KIRP), HDAC1 expression was found to be correlated with inflammatory cell infiltration. The levels of HDAC1 are expected to adapt to clinical adjuvant targeted therapy in most types of solid cancer.

Similar scaffold commercial drugs leucal (LEU), epirubicin (EPI), and lometrexol also displayed strong binding to the active site of MTHFD2...The interaction of breast cancer serum with high expression of MTHFD2 also showed an increase in binding of epirubicin in the presence of leucovorin...Further experimental studies are required to establish the potential mode of inhibition of the novel small ligands. Future in vivo trials may validate the effectiveness of the combinatorial therapy.

The patient underwent a multimodal treatment approach, including bladder-preserving surgery, 12 cycles of high-dose MRTK-2020 neoadjuvant chemotherapy [comprising actinomycin D, vincristine, doxorubicin, cyclophosphamide (AVDC), ifosfamide, carboplatin, and etoposide (ICE)], followed by adjuvant radiotherapy. Despite the limited evidence base, bladder-preserving surgeries, when feasible, should be considered and accompanied by adjuvant therapies for optimal outcomes. This case illustrates the potential for successful treatment of pure MRTs of the bladder using a combination of surgery, chemotherapy, and radiotherapy.

TCM displayed a potential enhanced anti-tumor efficacy of PD-1/PD-L1 inhibitors on six types of tumor including colon, breast, colorectal, melanoma, and bladder cancer in animals. However, due to significant heterogeneity in the included studies, caution should be exercised regarding the results. More high-quality randomized controlled animal experiments are need.

The study firstly presents a non-invasive method for identifying and detecting HER2 expression in BCa CTU images. It might not only reduce the cost and subjectivity of traditional HER2 testing but also provide a new technical method for the precise treatment of BCa.

Conclusion ESCO2 participates in regulating the immune infiltration and affecting the prognosis of patients in many cancers, especially in BLCA. ESCO2 may serve as a prognostic and immunotherapy biomarker in future treatment of human cancer.

Our study reveals the mechanism by which ANXA6 enhances cisplatin sensitivity and re-sensitizes resistant cells. The roles of PRRX1 and ANXA6 in cisplatin resistance offer new therapeutic targets to overcome cisplatin resistance in clinical practice.

In vitro, we found that Pld2-KO mouse TAMs had significantly enhanced proliferation, correlating closely with increased interleukin-1β (IL-1β) production. These results indicate that PLD2 suppresses BC progression by regulation of IL-1β secretion from TAMs in the TME, suggesting that PLD2 could serve as a potential therapeutic target for modifying the TME in BC.

P3, N=25, Active, not recruiting, Ferring Pharmaceuticals | Recruiting --> Active, not recruiting

In a recent clinical trial, a new super-agonist complex of IL-15 - N803, has shown promising results when used in combination with BCG to treat patients with bladder cancer who do not respond to BCG. Moreover, the sequential intravesical instillation of epirubicin (EPI), a first-line bladder cancer drug, followed by thermally activated 15&15Rα@VNP, could achieve further improved therapeutic responses, without causing significant side effects. Therefore, this study shows that 15&15Rα@VNP can be effectively used in the treatment of bladder cancer and can be used as a complementary therapy to chemotherapy agents, promising for potential clinical translation in bladder cancer treatment.

AURKB, GINS2, and UHRF1 have the potential to enhance postoperative management of NMIBC patients undergoing transurethral resection of bladder tumor (TURBT) and can predict immunotherapy response, establishing them as promising therapeutic targets.

The ToxoDB#9-type experimental group showed higher efficacy than the RH-type experimental group in inhibiting bladder cancer cell proliferation, reducing cell migration and invasion and promoting apoptosis. These results indicated that the culture supernatant of T. gondii tachyzoites could be a promising therapeutic agent for the treatment of bladder cancer.

Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.