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Loss of Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Tumor Microenvironment and Response to BCG Immunotherapy in a Murine Orthotopic Model of Bladder Cancer.
Int J Mol Sci
December 2024
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
Loss of the glutathione-S-transferases Theta 2 (Gstt2) expression is associated with an improved response to intravesical , Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC) patients who receive fewer BCG instillations. To delineate the cause, Gstt2 knockout (KO) and wildtype (WT) C57Bl/6J mice were implanted with tumors before treatment with BCG or saline. RNA was analyzed via single-cell RNA sequencing (scRNA-seq) and real-time polymerase chain reaction (RT-PCR).
View Article and Find Full Text PDFUltrasound irradiation in the presence of microbubbles may enhance the antitumor effect of chemotherapeutic agents against bladder cancer.
J Cancer
January 2025
Department of Urology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
Intravesical instillation of chemotherapy has been performed to reduce the risk of intravesical recurrence of bladder cancer. However, its antitumor effect is not necessarily sufficient, which may be partially due to inadequate delivery of intravesically administered chemotherapeutic agents to bladder tumors. Ultrasound irradiation to target tissues in the presence of microbubbles is a technique to transiently enhance cell membrane permeability and achieve efficient drug delivery to the desired sites without damage to non-target areas; this technique has been used in chemotherapy, immunotherapy, gene therapy, and radiotherapy for the treatment of various cancers.
View Article and Find Full Text PDFFDA Approval Summary: Nadofaragene firadenovec-vncg for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer.
Clin Cancer Res
December 2024
United States Food and Drug Administration, Silver Spring, Maryland, United States.
On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months.
View Article and Find Full Text PDFTHE STING AGONIST VB-85247 INDUCES DURABLE ANTITUMOR IMMUNE RESPONSES BY INTRAVESICAL ADMINISTRATION IN A NON-MUSCLE INVASIVE BLADDER CANCER.
Cancer Res
December 2024
Genesis Biotechnology Group, Hamilton, NJ, United States.
Bacillus Calmette-Guerin (BCG) is the current standard of care for non-muscle invasive bladder cancer (NMIBC), but recurrence is common. Additional therapeutic options are a major unmet medical need for treating unresponsive patients. Stimulator of Interferon Genes (STING) plays a central role in mounting innate and adaptive immune responses to tumor cells, and activation of STING is a promising immunotherapeutic approach.
View Article and Find Full Text PDFChemoresistance-motility signature of molecular evolution to chemotherapy in non-muscle-invasive bladder cancer and its clinical implications.
Cancer Lett
February 2025
Department of Biomedical Sciences, Dong-A University, Busan, 49315, South Korea; Department of Health Sciences, The Graduated of Dong-A University, Busan, 49315, South Korea. Electronic address:
Article Synopsis
- * The researchers created a 63-gene signature called Chemoresistance-Motility (CrM) to study how NMIBC evolves over time and used it to analyze 1,846 samples, revealing that early resistance stages are linked to increased cell movement and metastasis.
- * The study suggests that patients with high CrM scores have worse outcomes, ineffective responses to BCG and immune therapies, and identifies five alternative drugs to gemcitabine that may be effective, proposing a need for further validation of these findings.
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