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1.
Melanie A. Krook Julie W. Reeser Gabrielle Ernst Hannah Barker Max Wilberding Gary Li Hui-Zi Chen Sameek Roychowdhury 《British journal of cancer》2021,124(5):880
Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer 相似文献
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Arthur I. Kooyker Esther Toes-Zoutendijk Annemieke W.J. Opstal-van Winden Manon C.W. Spaander Maaike Buskermolen Hanneke J. van Vuuren Ernst J. Kuipers Folkert J. van Kemenade Chris Ramakers Maarten G.J. Thomeer Evelien Dekker Iris D. Nagtegaal Harry J. de Koning Monique E. van Leerdam Iris Lansdorp-Vogelaar 《International journal of cancer. Journal international du cancer》2020,147(4):1098-1106
The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round. 相似文献
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Straetmans Jos M. J. A. A. Stuut Marijn Wagemakers Sanne Hoebers Frank Kaanders Johannes H. A. M. Speel Ernst Jan M. Melchers Willem J. G. Slootweg Piet Kremer Bernd Lacko Martin Takes Robert P. 《European archives of oto-rhino-laryngology》2020,277(6):1753-1761
European Archives of Oto-Rhino-Laryngology - Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral... 相似文献
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Baettig Linda Baeumelt Andreas Ernst Jutta Boeker Heinz Grimm Simone Richter Andre 《Brain imaging and behavior》2020,14(6):2073-2083
Brain Imaging and Behavior - Oxytocin is both a hormone and a neurotransmitter and has been originally recognized for its role in childbirth and lactation. Later, it became widely known as a... 相似文献
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Cameron N. Johnstone Andrew D. Pattison Paul F. Harrison David R. Powell Peter Lock Matthias Ernst Robin L. Anderson Traude H. Beilharz 《International journal of cancer. Journal international du cancer》2020,147(1):230-243
Triple-negative breast cancer (TNBC) represents 10–20% of all human ductal adenocarcinomas and has a poor prognosis relative to other subtypes, due to the high propensity to develop distant metastases. Hence, new molecular targets for therapeutic intervention are needed for TNBC. We recently conducted a rigorous phenotypic and genomic characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that possess a range of intrinsic spontaneous metastatic capacities in vivo, ranging from nonmetastatic (MDA-MB-231_ATCC) to highly metastatic to lung, liver, spleen and spine (MDA-MB-231_HM). Gene expression profiling of primary tumours by RNA-Seq identified the fibroblast growth factor homologous factor, FGF13, as highly upregulated in aggressively metastatic MDA-MB-231_HM tumours. Clinically, higher FGF13 mRNA expression was associated with significantly worse relapse free survival in both luminal A and basal-like human breast cancers but was not associated with other clinical variables and was not upregulated in primary tumours relative to normal mammary gland. Stable FGF13 depletion restricted in vitro colony forming ability in MDA-MB-231_HM TNBC cells but not in oestrogen receptor (ER)-positive MCF-7 or MDA-MB-361 cells. However, despite augmenting MDA-MB-231_HM cell migration and invasion in vitro, FGF13 suppression almost completely blocked the spontaneous metastasis of MDA-MB-231_HM orthotopic xenografts to both lung and liver while having negligible impact on primary tumour growth. Together, these data indicate that FGF13 may represent a therapeutic target for blocking metastatic outgrowth of certain TNBCs. Further evaluation of the roles of individual FGF13 protein isoforms in progression of the different subtypes of breast cancer is warranted. 相似文献
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Schönfeld Michael H. Kabiri Reza Kniep Helge C. Meyer Lukas Sedlacik Jan Ernst Marielle Broocks Gabriel Faizy Tobias D. Cheng Bastian Thomalla Götz Fiehler Jens Hanning Uta 《Journal of neurology》2020,267(5):1401-1406
Journal of Neurology - To analyze the incidence of peripheral emboli after successful mechanical thrombectomy (MT) of intracranial large vessel occlusions (LVO). We performed a prospective analysis... 相似文献