Targeted therapies: Expanding the role of FGFR3 inhibition in urothelial carcinoma

Zengin, Zeynep Büşra; Chehrazi‐Raffle, Alex; Salgia, Nicholas; Muddasani, Ramya; Ali, Sana; Meza, Luís; Pal, Sumanta K.

doi:10.1016/j.urolonc.2021.10.003

Cited by 19 publications

(10 citation statements)

References 64 publications

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“…The aberrant activation of FGFR3 signaling has a well-established role in the development of BC [ 14 ]. Thus, FGFR3 has been proposed as a therapeutic target, and a number of inhibitors are currently in clinical trials [ 36 ]. Since RT-112 cells harbor an FGFR3-TACC3 gene fusion, which results in the constitutive activation of FGFR3 signaling [ 37 ], we further confirmed the expression level of FGFR3 in the SP-2-treated cells with a Western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade

et al. 2023

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Bladder cancer (BC) is one of the most prevalent cancers worldwide. However, the recurrence rate and five-year survival rate have not been significantly improved in advanced BC, and new therapeutic strategies are urgently needed. The anticancer activity of stellettin B (SP-2), a triterpene isolated from the marine sponge Rhabdastrella sp., was evaluated with the MTT assay as well as PI and Annexin V/7-AAD staining. Detailed mechanisms were elucidated through an NGS analysis, protein arrays, and Western blotting. SP-2 suppressed the viability of BC cells without severe toxicity towards normal uroepithelial cells, and it increased apoptosis with the activation of caspase 3/8/9, PARP, and γH2AX. The phosphorylation of FGFR3 and its downstream targets were downregulated by SP-2. Meanwhile, it induced autophagy in BC cells as evidenced by LC3-II formation and p62 downregulation. The inhibition of autophagy using pharmacological inhibitors or through an ATG5-knockout protected RT-112 cells from SP-2-induced cell viability suppression and apoptosis. In addition, the upregulation of DAPK2 mRNA and protein expression also contributed to SP-2-induced cytotoxicity and apoptosis. In RT-112 cells, an FGFR3-TACC3-knockout caused the downregulation of DAPK2, autophagy, and apoptosis. In conclusion, this is the first study demonstrating that SP-2 exhibits potent anti-BC activity by suppressing the FGFR3-TACC3/Akt/mTOR pathway, which further activates a novel autophagy/DAPK2/apoptosis signaling cascade.

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Section: Resultsmentioning

confidence: 99%

Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade

et al. 2023

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“…Targeted therapies offer a potentially promising strategy for precision therapy in BC. Other FGFR inhibitors have the following response rate: 25.4% for infigratinib (phase III PROOF 302 trial) [ 49 ], 25% pemigatinib (phase I/II FIGHT-101 study) [ 50 ], and 24% for rogaratinib [ 51 ]. There are several trials of ICI-EGRF inhibitor combination treatment (NORSE, FORT-2, FIGHT-205).…”

Section: Targeted Therapies In Ucmentioning

confidence: 99%

Advanced Bladder Cancer: Changing the Treatment Landscape

Bilim

Kuroki

Shirono

et al. 2022

JPM

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Bladder cancer is the 10th most common cancer type in the world. There were more than 573,000 new cases of bladder cancer in 2020. It is the 13th most common cause of cancer death with an estimated more than 212,000 deaths worldwide. Low-grade non-muscle-invasive bladder cancer (NMIBC) is usually successfully managed with transurethral resection (TUR) and overall survival for NMIBC reaches 90% according to some reports. However, long-term survival for muscle-invasive bladder cancer (MIBC) and metastatic bladder cancer remains low. Treatment options for bladder cancer have undergone a rapid change in recent years. Immune checkpoint inhibitors (ICI), targeted therapies, and antibody-drug conjugates are available now. As bladder cancer is genetically heterogeneous, the optimization of patient selection to identify those most likely to benefit from a specific therapy is an urgent issue in the treatment of patients with bladder cancer.

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“…In 2020, it was approved for treatment of mUC in China. Tyrosine kinase inhibitors (TKIs) have also shown promising efficacy in multiple malignancies, and several TKI agents targeting fibroblast growth factor receptors in UC are currently being studied, with promising findings from early phase clinical trials ( 14 ). Anlotinib is a newly invented oral small molecule TKI that inhibits tumor angiogenesis and cell proliferation ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

Case report: Significant benefits of tislelizumab combined with anlotinib in first-line treatment of metastatic renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation

Zhu

Yu²,

Wang³

et al. 2022

Front. Oncol.

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BackgroundRenal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation is a very dangerous malignant tumor and extremely rare in clinical practice. In general, these tumors with a dismal prognosis, and there is no standard treatment.Case presentationIn this case, an 81-year-old male patient was diagnosed with right renal pelvic carcinoma. After an open right radical nephroureterectomy, postoperative pathological examination showed infiltrating urothelial carcinoma with sarcomatoid differentiation. Overexpression of programmed death ligand-1 by immunohistochemistry. The carcinoma recurred 4.5 months after surgery. After informed, tislelizumab combined with anlotinib were used as first-line treatment. The patients showed a clinical partial response that lasted for 20 months.ConclusionThis case demonstrates the efficacy of tislelizumab combined with anlotinib in patients diagnosed with metastatic renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation. Moreover, to our knowledge, this is the first application of this treatment.

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Targeted therapies: Expanding the role of FGFR3 inhibition in urothelial carcinoma

Cited by 19 publications

References 64 publications

Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade

Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade

Advanced Bladder Cancer: Changing the Treatment Landscape

Case report: Significant benefits of tislelizumab combined with anlotinib in first-line treatment of metastatic renal pelvic urothelial carcinoma with sarcomatoid carcinoma differentiation

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