Urothelial Cancer

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.

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.

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.

This report emphasizes the crucial role of meticulous sampling and histopathologic examination of the fallopian tube, including the fimbriae, in all salpingectomy specimens. Furthermore, the case highlights the broad spectrum of morphologies encountered in HGSC, including mucinous differentiation. HGSC should be in the differential diagnosis when encountering mucin-producing high-grade carcinoma.

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.

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.

Notably, there was no difference in the incidence of immune-related AEs. In patients with mUC who received pembrolizumab, CRP flare-responders showed favorable oncological outcomes; therefore, BL CRP levels could predict oncological outcomes in CRP flare-responders.

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.

A selected subset of patients with advanced UC may experience long-term clinical benefit from anti-PD-(L)1 treatment. We identified prognostic factors that might be used for risk assessment and clinical trial stratification.

While TRPS1 remains a highly sensible immunohistochemical marker for confirming breast primary lesions, pathologists should be aware of its low specificity and incorporate complementary diagnostic methods in order to ensure accurate clinical management. Further research should focus on elucidating the molecular pathways regulating TRPS1 expression in various tumor types, which may better define its clinical utility.

Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC.

It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.

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.

P2, N=17, Active, not recruiting, National Cancer Institute (NCI) | N=209 --> 17 | Trial completion date: Jun 2024 --> Nov 2025

P2, N=210, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P2, N=23, Not yet recruiting, University of California, Irvine

P=N/A, N=0, Not yet recruiting, Peking University First Hospital; Peking University First Hospital

P=N/A, N=20, Not yet recruiting, Shanghai 10th People's Hospital; Shanghai 10th People's Hospital

P1, N=202, Recruiting, Synthekine | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

These findings underscore the pivotal role of CAF-related genes in prognostic prediction for BUC patients. Clinical decision-making and tailored therapeutics stand to benefit from these results, providing a valuable reference for future research endeavors.

Significant differences were observed in PFS and OS among the three groups (p<0.001 and p<0.001, respectively) and c-indices were 0.766 for PFS and 0.800 for OS. The risk classification using CRP and hypercalcemia is useful for predicting the outcomes of patients with advanced UC treated with EV.

P1, N=5, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=140 --> 5 | Trial completion date: Feb 2028 --> Mar 2025 | Trial primary completion date: Feb 2027 --> Mar 2025

P1, N=4, Terminated, Pfizer | Trial completion date: Aug 2025 --> Aug 2024 | Active, not recruiting --> Terminated; Strategic business decision

P=N/A, N=1000, Recruiting, Pacific Edge Limited | Trial completion date: Dec 2024 --> Mar 2025 | Trial primary completion date: Dec 2024 --> Mar 2025

Updated long-term follow-up from the ELARA trial continues to demonstrate robust durable responses >4 years post infusion, alongside a favorable safety profile. Correlative analyses suggest that most baseline high-risk disease characteristics (double-refractory disease, bulky disease, POD24, and high FLIPI) are not associated with inferior efficacy following tisagenlecleucel infusion in pts with r/r FL. Furthermore, high frequencies of MRD-negative status were achieved in a subset of evaluable pts.

P=N/A, N=420, Not yet recruiting, IRCCS San Raffaele

P1, N=47, Active, not recruiting, Bayer | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Mar 2025 --> Jun 2024

P1, N=95, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=96, Completed, Queen Mary University of London | Unknown status --> Completed

P2, N=58, Recruiting, Queen Mary University of London | Trial completion date: Dec 2024 --> May 2026 | Trial primary completion date: Jul 2023 --> May 2026

This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

This case demonstrates the feasibility of safely achieving stable cancer control in a kidney transplant patient with mUC without encountering graft rejection by using single-agent anti-PD-1 treatment.

P1, N=182, Active, not recruiting, Incyte Corporation | Trial completion date: Oct 2025 --> Dec 2024 | Trial primary completion date: Jul 2025 --> Aug 2024

P1, N=85, Active, not recruiting, Pfizer | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

P1, N=15, Terminated, Molecular Templates, Inc. | Active, not recruiting --> Terminated; Sponsor Termination

P1/2, N=20, Not yet recruiting, Ferring Pharmaceuticals

P2, N=43, Active, not recruiting, Taiho Oncology, Inc. | Trial primary completion date: Aug 2025 --> Mar 2024

BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.

The subgroup with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 had the highest PFS and OS improvements with pembrolizumab alone or with chemotherapy versus chemotherapy alone. These data suggest that TMB may be predictive of the response to pembrolizumab alone or with chemotherapy in advanced urothelial carcinoma.

The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody-drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.

P=N/A, N=150, Active, not recruiting, Mansoura University | Trial completion date: Jan 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024