Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy

Benjamin, David J.; Hsu, Robert

doi:10.3389/fimmu.2023.1258388

Cited by 7 publications

(3 citation statements)

References 45 publications

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“…The clinical trial NCT02792192 reported 3% complete response, 37% partial response and 39% stable disease (median progression-free survival of 5.5 months). Notably, FGFR2 and FGFR3 gene mutations are especially relevant; mutations FGFR2 N549H , FGFR3 Y373C;V555M , increase tumor immunity to FGFR-inhibitors [65,66].…”

Section: Intravesical Delivery Systemsmentioning

confidence: 99%

Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

Jaromin,

Konecki,

Kutwin

2024

Cancers

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Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients’ quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC.

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Section: Intravesical Delivery Systemsmentioning

confidence: 99%

Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

Jaromin,

Konecki,

Kutwin

2024

Cancers

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“…A subsequent version of the device, the TAR-210, has now been developed to deliver Erdafitinib, a selective pan-FGR tyroskin kinase inhibitor that targets the FGFR3 mutation, which has been identified as an oncogenic driver in urothelial cancer [40]. An oral formula-tion of the drug has been approved for use in patients with locally advanced or metastatic urothelial cancers.…”

Section: New Developments and Future Directionsmentioning

confidence: 99%

The Utility of Intraluminal Therapies in Upper Tract Urothelial Carcinoma: A Narrative Review

Tyrrell,

Chui,

Kealey

et al. 2024

Cancers

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Nephron sparing surgery (NSS) is considered for selected cases of upper tract urothelial carcinoma (UTUC) as it maintains renal function and avoids morbidity associated with radical nephroureterectomy (RNU). The appropriate selection of patients suitable for NSS without compromising oncological outcomes can sometimes be difficult, given the limitations of diagnostic modalities. Recurrence rates for UTUC can be as high as 36 to 54% after NSS. Intraluminal adjuvant therapy can be attempted following NSS to reduce recurrence, but delivery to the upper tract is more challenging than into the bladder. Bacillus Calmette-Guerin (BCG) and chemotherapy such as Mitomycin (MMC) have been administered via nephrostomy or ureteric catheter, which requires invasive/repeated instrumentation of the upper urinary tract. Drug delivery by reflux from bladder instillation along indwelling stents has also been tried but can potentially be unreliable. Recently, a gel formulation of mitomycin has been developed for the controlled exposure of the upper urinary tract to treatment over a number of hours. Drug-eluting stents to deliver chemotherapy to the upper urinary tract have been developed but have not yet entered clinical practice. Endoluminal phototherapy utilising an intravenous photosensitising agent is another novel approach that has recently been described. Intraluminal therapies may be beneficial in decreasing recurrence rates in UTUC, but currently have some limitations in their usage.

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“…Amplifications, mutations, and rearrangements of FGFRs have been frequently reported to drive tumor initiation and progression, especially in urothelial carcinoma (UC). In early-stage UC, over half of the cases show FGFR3 alterations [92], while around 20% of advanced/metastatic UC cases have FGFR3 mutations. Various FGFR kinase inhibitors have shown promise in targeting both cancer cells and the tumor microenvironment (TME).…”

Section: Fibroblast Growth Factor Receptors (Fgfrs)mentioning

confidence: 99%

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

Li,

Gong,

Zhou

et al. 2024

IJMS

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Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically for cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies and peptides, along with innovative approaches like the use of kinase degraders and protein kinase interaction inhibitors, which have recently demonstrated clinical progress and potential in overcoming resistance. Nevertheless, kinase-targeted strategies encounter significant hurdles, including drug resistance, which greatly impacts the clinical benefits for cancer patients, as well as concerning toxicity when combined with immunotherapy, which restricts the full utilization of current treatment modalities. Despite these challenges, the development of kinase inhibitors remains highly promising. The extensively studied tyrosine kinase family has 70% of its targets in various stages of development, while 30% of the kinase family remains inadequately explored. Computational technologies play a vital role in accelerating the development of novel kinase inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs underscore the importance of blood–brain barrier permeability for long-term patient benefits. This review provides a comprehensive summary of recent FDA-approved SMKIs based on their mechanisms of action and targets. We summarize the latest developments in potential new targets and explore emerging kinase inhibition strategies from a clinical perspective. Lastly, we outline current obstacles and future prospects in kinase inhibition.

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Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy

Cited by 7 publications

References 45 publications

Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

The Utility of Intraluminal Therapies in Upper Tract Urothelial Carcinoma: A Narrative Review

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

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