keyword
https://read.qxmd.com/read/37305616/significance-of-the-fgfr3-mutation-in-chinese-patients-with-bladder-cancer
#21
JOURNAL ARTICLE
Lanxiang Hao, Jiang Fang, Ran Xu, Shuo Liu, Guangcheng Luo, Xinjun Wang
BACKGROUND: Bladder cancer ( BC ) is the 10th most common malignancy worldwide. The high recurrence rates of BC lead to significant treatment challenges. With the development of molecular biology techniques, research has shown that gene abnormalities are closely related to the occurrence and development of BC . This study analyzed the detection results of gene mutations in the tissue samples of BC patients and explored the relationship between fibroblast growth factor receptor 3 ( FGFR3 ) and the prognosis and recurrence of BC ...
May 31, 2023: Translational Andrology and Urology
https://read.qxmd.com/read/37195586/urothelial-bladder-cancer-genomic-alterations-in-fibroblast-growth-factor-receptor
#22
JOURNAL ARTICLE
Maroun Bou Zerdan, Gennady Bratslavsky, Joseph Jacob, Jeffrey Ross, Richard Huang, Alina Basnet
BACKGROUND AND OBJECTIVE: Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response. METHODS: There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling...
May 17, 2023: Molecular Diagnosis & Therapy
https://read.qxmd.com/read/37151354/correlation-between-fibroblast-growth-factor-receptor-mutation-programmed-death-ligand-1-expression-and-survival-in-urinary-bladder-cancer-based-on-real-world-data
#23
JOURNAL ARTICLE
Janos Revesz, Boglarka Posfai, Laszlo Pajor, Timea Papdan, Linda Varga, Viktor R Paczona, Zoltan Varga, Farkas Sukosd, Aniko Maraz
Background: Programmed cell death (PD)-1/PD-ligand 1 (PD-L1) inhibitors have made a breakthrough in the therapy of advanced urothelial bladder cancer (UBC). The impact of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the effectiveness of PD-L1 treatment remains still unclear. Objective: Our study aimed to investigate the frequency of FGFR mutations at different tumor stages, and their relation to PD-L1 status and survival. Methods: 310 patients with urothelial bladder cancer and subsequent radical cystectomy were included in a retrospective study over a 10-year study period at the University of Szeged, Hungary...
2023: Pathology Oncology Research: POR
https://read.qxmd.com/read/37124509/case-report-pd-l1-negative-advanced-bladder-cancer-effectively-treated-with-anlotinib-and-tislelizumab-a-report-of-two-cases
#24
Teng Li, Wuyun Hu, Lan Jin, Xianghua Yin, Dongxu Kang, Longzhen Piao
Second-line treatment for metastatic or locally advanced urothelial cancer (UC) is limited. Immunotherapy is approved as a second-line treatment for metastatic UC. Its use as a first-line agent is limited to patients who are ineligible for cisplatin-based treatments. The fibroblast growth factor receptor (FGFR) inhibitor, erdafitinib, can be applied as a third-line approach after the failure of these prior treatments in eligible patients. Therefore, it is especially important to combine limited drugs for second-line treatment of advanced or metastatic UC...
2023: Frontiers in Oncology
https://read.qxmd.com/read/37000035/fight-102-a-phase-1-study-of-pemigatinib-in-japanese-patients-with-advanced-malignancies
#25
JOURNAL ARTICLE
Yukata Fujiwara, Yasutoshi Kuboki, Masayuki Furukawa, Nobumasa Mizuno, Hiroki Hara, Tatsuya Ioka, Makoto Ueno, Yasuo Takahashi, Shunji Takahashi, Shinji Takeuchi, Christine Lihou, Tao Ji, Chenwei Tian, Toshio Shimizu
BACKGROUND: FIGHT-102 was a phase 1, dose-escalation, dose-expansion study of pemigatinib in Japanese patients with advanced solid tumors. Here, we report safety, tolerability, and preliminary efficacy of pemigatinib from FIGHT-102. METHODS: Patients (≥20 years old) self-administered oral pemigatinib 9, 13.5, or 18 mg QD on intermittent dosing (Part 1) or 13.5 mg QD intermittent or continuous dosing (Part 2). A dosing cycle was 21 days (2 weeks on/1 week off or 21 continuous days)...
March 31, 2023: Cancer Medicine
https://read.qxmd.com/read/36966497/evolving-systemic-management-of-urothelial-cancers
#26
REVIEW
Wei Shen Tan, Mae-Yen Tan, Omar Alhalabi, Matthew T Campbell, Ashish M Kamat, Jianjun Gao
PURPOSE OF REVIEW: Bladder cancer is the 12th most common cancer worldwide. Historically, the systemic management of urothelial carcinoma has been confined to platinum-based chemotherapy. In this review, we discuss the evolving landscape of systemic treatment for urothelial carcinoma. RECENT FINDINGS: Since 2016, when the Food and Drug Administration approved the first immune checkpoint inhibitor (CPI), programmed cell death 1 and programmed cell death ligand 1 inhibitors have been evaluated in the nonmuscle invasive bladder cancer, localized muscle invasive bladder cancer as well as advanced/metastatic bladder cancer settings...
May 1, 2023: Current Opinion in Oncology
https://read.qxmd.com/read/36943397/p4ha2-mediated-hif-1%C3%AE-stabilization-promotes-erdafitinib-resistance-in-fgfr3-alteration-bladder-cancer
#27
JOURNAL ARTICLE
Xuexiang Li, Yunxue Li, Bing Liu, Liang Chen, Fang Lyu, Pu Zhang, Qingliu He, Lulin Cheng, Chunyu Liu, Yarong Song, Yifei Xing
Erdafitinib is a novel fibroblast growth factor receptor (FGFR) inhibitor that has shown great therapeutic promise for solid tumor patients with FGFR3 alterations, especially in urothelial carcinoma. However, the mechanisms of resistance to FGFR inhibitors remain poorly understood. In this study, we found Erdafitinib could kill cells by inducing incomplete autophagy and increasing intracellular reactive oxygen species levels. We have established an Erdafitinib-resistant cell line, RT-112-RS. whole transcriptome RNA sequencing (RNA-Seq) and Cytospace analysis performed on Erdafitinib-resistant RT-112-RS cells and parental RT-112 cells introduced P4HA2 as a linchpin to Erdafitinib resistance...
April 2023: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/36898352/role-of-fgfr3-in-bladder-cancer-treatment-landscape-and-future-challenges
#28
REVIEW
Claudia Maria Ascione, Fabiana Napolitano, Daniela Esposito, Alberto Servetto, Stefania Belli, Antonio Santaniello, Sarah Scagliarini, Felice Crocetto, Roberto Bianco, Luigi Formisano
Bladder cancer is a heterogeneous malignancy and is responsible for approximately 3.2% of new diagnoses of cancer per year (Sung et al., 2021). Fibroblast Growth Factor Receptors (FGFRs) have recently emerged as a novel therapeutic target in cancer. In particular, FGFR3 genomic alterations are potent oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR inhibitors. Indeed, overall ∼50% of bladder cancers have somatic mutations in the FGFR3 -coding sequence (Cappellen et al...
April 2023: Cancer Treatment Reviews
https://read.qxmd.com/read/36780330/oncogenic-driver-fgfr3-tacc3-requires-five-coiled-coil-heptads-for-activation-and-disulfide-bond-formation-for-stability
#29
JOURNAL ARTICLE
Clark G Wang, Malalage N Peiris, April N Meyer, Katelyn N Nelson, Daniel J Donoghue
FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers; these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity...
February 11, 2023: Oncotarget
https://read.qxmd.com/read/36765525/current-and-future-landscape-of-perioperative-treatment-for-muscle-invasive-bladder-cancer
#30
REVIEW
Jorge Esteban-Villarrubia, Javier Torres-Jiménez, Carolina Bueno-Bravo, Rebeca García-Mondaray, José Daniel Subiela, Pablo Gajate
Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard of care for muscle-invasive bladder cancer (MIBC). However, less than half of patients are candidates for this treatment, and 50% will develop metastatic disease. Adjuvant chemotherapy could be offered if neoadjuvant treatment has not been administered for suitable patients. It is important to reduce the risk of systemic recurrence and improve the prognosis of localized MIBC. Systemic therapy for metastatic urothelial carcinoma has evolved in recent years...
January 17, 2023: Cancers
https://read.qxmd.com/read/36729099/derazantinib-a-fibroblast-growth-factor-receptor-inhibitor-inhibits-colony-stimulating-factor-receptor-1-in-macrophages-and-tumor-cells-and-in-combination-with-a-murine-programmed-cell-death-ligand-1-antibody-activates-the-immune-environment-of-murine-syngeneic
#31
JOURNAL ARTICLE
Mahmoud El Shemerly, Elisa Zanini, Marc Lecoultre, Paul R Walker, Laurenz Kellenberger, Heidi A Lane, Paul M J McSheehy
Derazantinib (DZB) is an inhibitor of the fibroblast growth factor receptors 1-3 (FGFRi) with similar potency against colony-stimulating factor receptor-1 (CSF1R), a protein important in the recruitment and function of tumor-associated macrophages. DZB inhibited pCSF1R in the macrophage cell line RAW264.7, and tumor cells GDM-1 and DEL, and had the same potency in HeLa cells transiently over-expressing FGFR2. DZB exhibited similar potency against pCSF1R expressed by isolated murine macrophages, but as in the cell lines, specific FGFRi were without significant CSF1R activity...
December 19, 2022: Anti-cancer Drugs
https://read.qxmd.com/read/36675289/genetic-interference-of-fgfr3-impedes-invasion-of-upper-tract-urothelial-carcinoma-cells-by-alleviating-ras-mapk-signal-activity
#32
JOURNAL ARTICLE
Gong-Kai Huang, Chao-Cheng Huang, Chih-Hsiung Kang, Yuan-Tso Cheng, Po-Ching Tsai, Ying-Hsien Kao, Yueh-Hua Chung
Upper tract urothelial cancer (UTUC) is a less common disease in Western countries but has a high level of prevalence in Asian populations. Compared to bladder cancer, unique etiologic and genomic factors are involved in UTUC. Fibroblast growth factor receptor 3 (FGFR3) up-regulation has been proposed as a promising target for bladder cancer therapy. In this study, we aimed to profile the expression of FGFR3 in Asian and Caucasian UTUC tissues and to evaluate the in vitro therapeutic efficacy of small interference RNA (siRNA)-mediated FGFR3 silencing in UTUC treatment...
January 16, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36653279/actionable-genomic-landscapes-from-a-real-world-cohort-of-urothelial-carcinoma-patients
#33
JOURNAL ARTICLE
Thomas Gerald, Vitaly Margulis, Xiaosong Meng, Aditya Bagrodia, Suzanne Cole, Qian Qin, S Greg Call, Elizabeth Mauer, Yair Lotan, Solomon L Woldu
BACKGROUND: Recent targeted therapies for advanced and metastatic urothelial cancer have generated enthusiasm, but the actionable genomic landscape of early-stage disease remains largely unknown. Here, we utilized a large, real-world cohort to comprehensively investigate the incidence of genetic alterations with potential therapeutic implications at all stages of bladder cancer. MATERIALS AND METHODS: We retrospectively analyzed next-generation sequencing (NGS) data from 1,562 bladder cancer patients (stages I-IV) with formalin-fixed, paraffin-embedded tumor biopsies sequenced using the Tempus xT solid tumor assay...
March 2023: Urologic Oncology
https://read.qxmd.com/read/36643309/characterizing-treatment-resistance-in-muscle-invasive-bladder-cancer-using-the-chicken-egg-chorioallantoic-membrane-patient-derived-xenograft-model
#34
JOURNAL ARTICLE
Hugo Villanueva, Gabrielle A Wells, Malachi T Miller, Mariana Villanueva, Ravi Pathak, Patricia Castro, Michael M Ittmann, Andrew G Sikora, Seth P Lerner
BACKGROUND: Non-metastatic muscle invasive urothelial bladder cancer (MIBC) has a poor prognosis and standard of care (SOC) includes neoadjuvant cisplatin-based chemotherapy (NAC) combined with cystectomy. Patients receiving NAC have at best <10% improvement in five-year overall survival compared to cystectomy alone. This major clinical problem underscores gaps in our understanding of resistance mechanisms and a need for reliable pre-clinical models. The chicken embryo chorioallantoic membrane (CAM) represents a rapid, scalable, and cost-effective alternative to immunocompromised mice for establishing patient-derived xenografts (PDX) in vivo ...
December 2022: Heliyon
https://read.qxmd.com/read/36640858/inhibition-of-bladder-cancer-growth-with-homoharringtonine-by-inactivating-integrin-%C3%AE-5-%C3%AE-1-fak-src-axis-a-novel-strategy-for-drug-application
#35
JOURNAL ARTICLE
Qiushuang Wu, Pengchen Chen, Junnan Li, Ziqi Lin, Qingwen Zhang, Hang Fai Kwok
The application of immune checkpoint inhibitors and FGFR protein tyrosine kinase inhibitors have made a tremendous breakthrough in bladder cancer therapy. However, inadequate drug responses and drug resistance interfere with successful treatment outcomes. For a new drug to enter the market, there is a long development cycle with high costs and low success rates. Repurposing previously Food and Drug Administration (FDA)-approved medications and using novel drug discovery strategies may be an optimal approach...
February 2023: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/36462464/pan-tumor-landscape-of-fibroblast-growth-factor-receptor-1-4-genomic-alterations
#36
JOURNAL ARTICLE
K Murugesan, A Necchi, T C Burn, O Gjoerup, R Greenstein, M Krook, J A López, M Montesion, H Nimeiri, A R Parikh, S Roychowdhury, S Schwemmers, I M Silverman, A Vogel
BACKGROUND: Selective tyrosine kinase inhibitors targeting fibroblast growth factor receptor (FGFR) 1-4 genomic alterations are in development or have been approved for FGFR-altered cancers (e.g. bladder cancer and advanced intrahepatic cholangiocarcinoma). Understanding FGFR inhibitor-resistance mechanisms is increasingly relevant; we surveyed the pan-tumor landscape of FGFR1-4 genomic alterations [short variants (SVs), gene rearrangements (REs), and copy number alterations (CNAs)], including their association with tumor mutational burden (TMB) and the genomic comutational landscape...
December 2022: ESMO Open
https://read.qxmd.com/read/36385700/development-of-resistance-to-fgfr-inhibition-in-urothelial-carcinoma-via-multiple-pathways-in-vitro
#37
JOURNAL ARTICLE
Geoffrey A Pettitt, Carolyn D Hurst, Zubeda Khan, Helen R McPherson, Matthew C Dunning, Olivia Alder, Fiona M Platt, Emma V I Black, Julie E Burns, Margaret A Knowles
Alterations of fibroblast growth factor receptors (FGFRs) are common in bladder and other cancers and result in disrupted signalling via several pathways. Therapeutics that target FGFRs have now entered the clinic, but in common with many cancer therapies, resistance develops in most cases. To model this we derived resistant sublines of two FGFR-driven bladder cancer cell lines by long term culture with the FGFR inhibitor PD173074 and explored mechanisms using expression profiling and whole exome sequencing...
November 16, 2022: Journal of Pathology
https://read.qxmd.com/read/36356320/discovery-of-potent-and-selective-inhibitors-of-wild-type-and-gatekeeper-mutant-fibroblast-growth-factor-receptor-fgfr-2-3
#38
JOURNAL ARTICLE
Artem Shvartsbart, Jeremy J Roach, Michael R Witten, Holly Koblish, Jennifer J Harris, Maryanne Covington, Rodrigo Hess, Luping Lin, Michelle Frascella, Lisa Truong, Lynn Leffet, Patricia Conlen, Elham Beshad, Ron Klabe, Kamna Katiyar, Laura Kaldon, Ruth Young-Sciame, Xin He, Susan Petusky, Kwang-Jong Chen, April Horsey, Hsiang-Ting Lei, Leslie B Epling, Marc C Deller, Oleg Vechorkin, Wenqing Yao
Upregulation of the fibroblast growth factor receptor (FGFR) signaling pathway has been implicated in multiple cancer types, including cholangiocarcinoma and bladder cancer. Consequently, small molecule inhibition of FGFR has emerged as a promising therapy for patients suffering from these diseases. First-generation pan-FGFR inhibitors, while highly effective, suffer from several drawbacks. These include treatment-related hyperphosphatemia and significant loss of potency for the mutant kinases. Herein, we present the discovery and optimization of novel FGFR2/3 inhibitors that largely maintain potency for the common gatekeeper mutants and have excellent selectivity over FGFR1...
November 10, 2022: Journal of Medicinal Chemistry
https://read.qxmd.com/read/36307559/sustained-response-on-sequential-anti-fgfr-therapy-in-metastatic-gall-bladder-cancer-a-case-report-and-literature-review
#39
JOURNAL ARTICLE
Hardik Sheth, Sewanti Limaye, Prashant Kumar, Aditya Shreenivas
PURPOSE: Advanced gall bladder cancer (GBC) is an aggressive disease, and there is no consensus on treatment options beyond first-line chemotherapy. We report a case of an elderly male with FGFR2-altered advanced adenocarcinoma of the gallbladder who failed two prior lines of chemotherapy but had sustained response and stable disease on sequential FGFR-directed targeted therapy. DESIGN: We describe a case of FGFR2-altered metastatic adenocarcinoma of the gallbladder who failed two prior lines of chemotherapy...
October 28, 2022: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/36186672/immunotherapy-with-checkpoint-inhibitors-in-fgfr-altered-urothelial-carcinoma
#40
REVIEW
David J Benjamin, Nataliya Mar, Arash Rezazadeh Kalebasty
The treatment landscape of metastatic urothelial cancer (mUC) remained unchanged for over 30 years until the approval of immune checkpoint inhibitors (ICIs) in 2016. Since then, several ICIs have been approved for the treatment of mUC. In addition, recent molecular characterization of bladder cancer has revealed several subtypes, including those harboring fibroblast growth factor receptor (FGFR) mutations and fusion proteins. Erdafitinib, a pan-FGFR inhibitor, was approved for the treatment of metastatic/advanced UC in 2019...
2022: Clinical Medicine Insights. Oncology
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