Targeting of BRD4 with JQ1, combined with mitomycin C as a novel combination therapy for non-muscle invasive bladder cancer

Simm, C.; Caridis, Anna-Maria; Maio, Anna; Knowles, P. F.; Gorman, Blythe; Jones, R. Watson; Ward, Douglas G.; Oppermann, Udo; Bountra, C.; Khanim, Farhat L.; Bryan, Richard T.

doi:10.1016/s1569-9056(18)31300-9

Cited by 2 publications

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“…Developments in technology for genomic analyses have identified molecular subtypes of NMIBC, potentially permitting the future stratification of BCa treatments and the subsequent delivery of personalised intravesical therapeutic approaches in the management of NMIBC ( 12 ). Although such precision medicine in NMIBC has not yet been realised, several drugs that target and “reset” genome-wide epigenetic modifications are being investigated in pre-clinical studies, and have shown extremely promising results in pre-clinical BCa models ( 129 , 130 ).…”

Section: Discussionmentioning

confidence: 99%

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

et al. 2022

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IntroductionNon-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.MethodsPubMed, ClinicalTrials.gov and Cochrane Library searches were undertaken. Systematic reviews, meta-analyses, randomised controlled trials, single-arm clinical trials and national/international conference proceedings were included.ResultsNovel intravesical drugs, including chemotherapeutic agents, immune checkpoint inhibitors, monoclonal antibodies and gene therapies, have demonstrated varying efficacy in the treatment of NMIBC. Current evidence for the majority of treatments is mostly limited to single-arm trials in patients with recurrent NMIBC. Various novel methods of drug delivery have also been investigated, with encouraging preliminary results supporting the intravesical delivery of hyperthermic MMC and MMC hydrogel formulations.ConclusionsNovel therapeutic agents and drug delivery systems will be important in the future intravesical management of NMIBC. As our understanding of the molecular diversity of NMIBC develops, molecular subtyping will become fundamental in the personalisation of intravesical treatments. Further randomised studies are urgently required to investigate the efficacy of novel intravesical treatments and novel regimens, in comparison to current standards-of-care, particularly in the context of international BCG shortages.

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Section: Discussionmentioning

confidence: 99%

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

et al. 2022

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“…Regarding BC, the (+)-JQ1 inhibitor induces autophagy through activation of the LKB1/AMPK pathway, contributing to the inhibition of proliferation of BC cell lines in vitro (Li et al, 2019). In combination with Mitomicyn C, (+)-JQ1 enhances cell death, which offers the possibility of a dose reduction of the chemotherapeutic agent (Simm et al, 2018). Hölscher et al had also shown significant synergistic effects on the induction of apoptosis in urothelial cancer cells by treatment with (+)-JQ1 and Romidepsin, an HDAC inhibitor (HDACi), thus suggesting a promising new combination therapy approach for urothelial cancer (Hölscher et al, 2018).…”

Section: New Therapies In Epigeneticsmentioning

confidence: 99%

Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet

et al. 2019

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Bladder cancer (BC) is the most common neoplasia of the urothelial tract. Due to its high incidence, prevalence, recurrence and mortality, it remains an unsolved clinical and social problem. The treatment of BC is challenging and, although immunotherapies have revealed potential benefit in a percentage of patients, it remains mostly an incurable disease at its advanced state. Epigenetic alterations, including aberrant DNA methylation, altered chromatin remodeling and deregulated expression of non-coding RNAs are common events in BC and can be driver events in BC pathogenesis. Accordingly, these epigenetic alterations are now being used as potential biomarkers for these disorders and are being envisioned as potential therapeutic targets for the future management of BC. In this review, we summarize the recent findings in these emerging and exciting new aspects paving the way for future clinical treatment of this disease.

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Targeting of BRD4 with JQ1, combined with mitomycin C as a novel combination therapy for non-muscle invasive bladder cancer

Cited by 2 publications

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Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet

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