Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas
Cholangiocarcinomas and urothelial carcinomas are lethal tumors worldwide and only a minority of patients are eligible for surgery at diagnosis. Moreover, patients are poorly responsive to current therapeutic strategies, including chemotherapy, radiotherapy, immunotherapy, and multimodality treatmen...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402306749X |
| _version_ | 1827803133498097664 |
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| author | Demi Wekking Andrea Pretta Serafina Martella Alessandra Pia D'Agata Joanna Joeun Choe Nerina Denaro Cinzia Solinas Mario Scartozzi |
| author_facet | Demi Wekking Andrea Pretta Serafina Martella Alessandra Pia D'Agata Joanna Joeun Choe Nerina Denaro Cinzia Solinas Mario Scartozzi |
| author_sort | Demi Wekking |
| collection | DOAJ |
| description | Cholangiocarcinomas and urothelial carcinomas are lethal tumors worldwide and only a minority of patients are eligible for surgery at diagnosis. Moreover, patients are poorly responsive to current therapeutic strategies, including chemotherapy, radiotherapy, immunotherapy, and multimodality treatments. Recently, several advances have been made in precision medicine and these results are modifying the treatment paradigm for patients diagnosed with cholangiocarcinomas and urothelial carcinoma. These histotypes exhibit a high rate of multiple fibroblast growth factor receptor (FGFR) genetic alterations and numerous preclinical and clinical studies support FGFR as a highly attractive novel therapeutic target. Moreover, identifying specific genetic alterations may predict the tumor's response to conventional and novel FGFR-targeted drugs. Recent clinical studies showed promising data for FGFR-targeted therapy in reducing tumor volume and led to the United States Food and Drug Administration (FDA) approval of, e.g., pemigatinib, infigratinib, futibatinib, and erdafitinib. Moreover, FGFR inhibitors show promising results in the first-line setting of cholangiocarcinomas and urothelial carcinomas. Pemigatinib (FIGHT-302) and futibatinib (FOENIX-CAA3) are being evaluated in phase III trials that compare these agents to current first-line gemcitabine and cisplatin in FGFR2-rearranged cholangiocarcinoma. However, complexity in targeting the FGFR signaling pathway is observed. Herein, we describe the characteristics of the FDA-approved and other investigational FGFR-targeted therapeutics, evaluate the most recent preclinical and clinical studies focusing on targeting FGFR genomic alterations in the treatment of cholangiocarcinomas and urothelial cancer, and provide insight into factors involved in response and (acquired) resistance to FGFR inhibition. |
| first_indexed | 2024-03-11T20:50:12Z |
| format | Article |
| id | doaj.art-055bbcfc3c534fc5b5410d296cacf290 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T20:50:12Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-055bbcfc3c534fc5b5410d296cacf2902023-10-01T06:00:01ZengElsevierHeliyon2405-84402023-09-0199e19541Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomasDemi Wekking0Andrea Pretta1Serafina Martella2Alessandra Pia D'Agata3Joanna Joeun Choe4Nerina Denaro5Cinzia Solinas6Mario Scartozzi7Amsterdam UMC, Location Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Corresponding author.Medical Oncology Unit, University Hospital and University of Cagliari, ItalyMedical Oncology, University Hospital Policlinico G.Rodolico-San Marco, 95123, Catania, ItalyMedical Oncology Unit, University Hospital and University of Cagliari, ItalyCancer Outcomes Research and Education, Massachusetts General Hospital, Boston, MA, USAMedical Oncology, Policlinico Milano, ItalyMedical Oncology AOU Cagliari Policlinico Duilio Casula, Monserrato, CA, Italy; Corresponding author.Medical Oncology Unit, University Hospital and University of Cagliari, Italy; Medical Oncology AOU Cagliari Policlinico Duilio Casula, Monserrato, CA, ItalyCholangiocarcinomas and urothelial carcinomas are lethal tumors worldwide and only a minority of patients are eligible for surgery at diagnosis. Moreover, patients are poorly responsive to current therapeutic strategies, including chemotherapy, radiotherapy, immunotherapy, and multimodality treatments. Recently, several advances have been made in precision medicine and these results are modifying the treatment paradigm for patients diagnosed with cholangiocarcinomas and urothelial carcinoma. These histotypes exhibit a high rate of multiple fibroblast growth factor receptor (FGFR) genetic alterations and numerous preclinical and clinical studies support FGFR as a highly attractive novel therapeutic target. Moreover, identifying specific genetic alterations may predict the tumor's response to conventional and novel FGFR-targeted drugs. Recent clinical studies showed promising data for FGFR-targeted therapy in reducing tumor volume and led to the United States Food and Drug Administration (FDA) approval of, e.g., pemigatinib, infigratinib, futibatinib, and erdafitinib. Moreover, FGFR inhibitors show promising results in the first-line setting of cholangiocarcinomas and urothelial carcinomas. Pemigatinib (FIGHT-302) and futibatinib (FOENIX-CAA3) are being evaluated in phase III trials that compare these agents to current first-line gemcitabine and cisplatin in FGFR2-rearranged cholangiocarcinoma. However, complexity in targeting the FGFR signaling pathway is observed. Herein, we describe the characteristics of the FDA-approved and other investigational FGFR-targeted therapeutics, evaluate the most recent preclinical and clinical studies focusing on targeting FGFR genomic alterations in the treatment of cholangiocarcinomas and urothelial cancer, and provide insight into factors involved in response and (acquired) resistance to FGFR inhibition.http://www.sciencedirect.com/science/article/pii/S240584402306749XFibroblast growth factor receptor inhibitorsCholangiocarcinomaBladder cancerFGFR genetic alterationsTargeted therapyAcquired resistance |
| spellingShingle | Demi Wekking Andrea Pretta Serafina Martella Alessandra Pia D'Agata Joanna Joeun Choe Nerina Denaro Cinzia Solinas Mario Scartozzi Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas Heliyon Fibroblast growth factor receptor inhibitors Cholangiocarcinoma Bladder cancer FGFR genetic alterations Targeted therapy Acquired resistance |
| title | Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas |
| title_full | Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas |
| title_fullStr | Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas |
| title_full_unstemmed | Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas |
| title_short | Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas |
| title_sort | fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas |
| topic | Fibroblast growth factor receptor inhibitors Cholangiocarcinoma Bladder cancer FGFR genetic alterations Targeted therapy Acquired resistance |
| url | http://www.sciencedirect.com/science/article/pii/S240584402306749X |
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